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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.

Background Survival rate for oral tongue squamous cell carcinoma (OTSCC) is still poor and, despite Tumor-Node-Metastasis staging system has been recently updated, patients included under the same stage still show difference in prognosis. Perineural invasion (PNI) emerged to be an indicator of tumor aggressive behavior and unfortunate events. In this study, we investigate the clinic and prognostic value of PNI in a cohort of OTSCC patients. Methods About 200 patients with OTSCC were retrospectively evaluated the presence of PNI. PNI was furtherly descripted as uni-/multifocal and as intra-/peritumoral. Disease-Specific and Relapse-Free Survival (DSS; RFS) were estimated; moreover, we included PNI in the current AJCC 8th Staging System, improving the prognostication model. Results Perineural invasion was found in 40.5% of patients. Intratumoral PNI predicted patients at high risk of being diagnosed with lymph-node metastasis. Tumors with positive PNI reported a worse DSS (Hazard Ratio=1.878, p-value = 0.008). Moreover, patients exhibiting both multifocal intra- and peritumoral PNI reported poorest DSS (Hazard Ratio = 2.409, p-value = 0.010). Patients were reclassified in a new staging system in case of multifocal PNI, providing better stratification capacity. Conclusions Perineural invasion might serve as an additional prognostic factor in OTSCC, and by integrating PNI in the staging system, further improvements in prognostication might be reached.

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.

Background Although oral P2Y12 inhibitors are key in the management of patients with non-ST elevation acute coronary syndrome (NSTE-ACS), the optimal timing of their administration is not well defined. Objective to compare downstream and upstream oral P2Y12 inhibitors administration strategies in NSTE-ACS patients undergoing invasive management. Methods We performed a randomized, adaptive, open-label, multi-center, 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 (PCI) were further randomized to receive ticagrelor or prasugrel. The primary hypothesis was superiority of the downstream over the upstream strategy on the combination of efficacy and safety events (net clinical benefit). Results We randomized 1449 patients to downstream or upstream oral P2Y12 inhibitor administration. A prespecified stopping rule for futility at interim analysis led the trial to be stopped. The rate of the primary endpoint, a composite of death due to vascular causes, non-fatal myocardial infarction or non-fatal stroke, and Bleeding Academic Research Consortium (BARC) type 3, 4 and 5 bleedings through day 30, did not differ significantly between the downstream and upstream groups (Absolute Risk Reduction (ARR%) -0.46 [-2.90; 1.90]).These results were confirmed among patients undergoing PCI (72% of population) and regardless of the timing of coronary angiography (within or after 24 hours from enrolment). Conclusions Downstream and upstream oral P2Y12 inhibitors administration strategies were associated with low incidence of ischemic and bleeding events and minimal numerical difference of event rates between treatment groups. These findings led to premature interruption of the trial and suggest the unlikelihood of enhanced efficacy of one strategy over the other. [Funded by the Italian Society of Interventional Cardiology (SICI-GISE)]

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

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.

BACKGROUND: The COVID-19 pandemic has put several healthcare systems under severe pressure. The present analysis investigates how the first wave of the COVID-19 pandemic affected the myocardial infarction (MI) network of Emilia-Romagna (Italy). METHODS: Based on Emilia-Romagna mortality registry and administrative data from all the hospitals from January 2017 to June 2020, we analysed: i) temporal trend in MI hospital admissions; ii) characteristics, management, and 30-day mortality of MI patients; iii) out-of-hospital mortality for cardiac cause. FINDINGS: Admissions for MI declined on February 22, 2020 (IRR -19.5%, 95%CI from -8.4% to -29.3%, p=0.001), and further on March 5, 2020 (IRR -21.6%, 95%CI from -9.0% to -32.5%, p=0.001). The return to pre-COVID-19 MI-related admission levels was observed from May 13, 2020 (IRR 34.3%, 95%CI 20.0%-50.2%, p

One of the objectives of current researches is to be able to customize the treatment of cancer patients. This can be possible only by better stratifying patients based on the most significant prognostic factors [1]. [...]

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.

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 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.

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.

Background It remains unclear whether radial access (RA), compared with femoral access (FA), mitigates the risk of acute kidney injury (AKI). Objectives The authors assessed the incidence of AKI in patients with acute coronary syndrome (ACS) enrolled in the MATRIX-Access (Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of Angiox) trial. Methods Among 8,404 patients, 194 (2.3%) were excluded due to missing creatinine values, no or an incomplete coronary angiogram, or previous dialysis. The primary AKI-MATRIX endpoint was AKI, defined as an absolute (>0.5 mg/dl) or a relative (>25%) increase in serum creatinine (sCr). Results AKI occurred in 634 patients (15.4%) with RA and 712 patients (17.4%) with FA (odds ratio [OR]: 0.87; 95% confidence interval [CI]: 0.77 to 0.98; p = 0.0181). A >25% sCr increase was noted in 633 patients (15.4%) with RA and 710 patients (17.3%) with FA (OR: 0.87; 95% CI: 0.77 to 0.98; p = 0.0195), whereas a >0.5 mg/dl absolute sCr increase occurred in 175 patients (4.3%) with RA versus 223 patients (5.4%) with FA (OR: 0.77; 95% CI: 0.63 to 0.95; p = 0.0131). By implementing the Kidney Disease Improving Global Outcomes criteria, AKI was 3-fold less prevalent and trended lower with RA (OR: 0.85; 95% CI: 0.70 to 1.03; p = 0.090), with stage 3 AKI occurring in 28 patients (0.68%) with RA versus 46 patients (1.12%) with FA (p = 0.0367). Post-intervention dialysis was needed in 6 patients (0.15%) with RA and 14 patients (0.34%) with FA (p = 0.0814). Stratified analyses suggested greater benefit with RA than FA in patients at greater risk for AKI. Conclusions In ACS patients who underwent invasive management, RA was associated with a reduced risk of AKI compared with FA. (Minimizing Adverse Haemorrhagic Events by TRansradial Access Site and Systemic Implementation of angioX [MATRIX]; NCT01433627 )

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.

The aim of this study was to compare the oral health status and salivary antioxidant system between patients diagnosed with anorexia nervosa (AN) and healthy controls. A total of 25 female AN patients and 25 matched healthy controls were enrolled. Clinical parameters and saliva samples were collected for each patient. Two questionnaires to investigate oral health and hygiene were administered. Superoxide Dismutase (SOD) activity and High Reactive Oxygen Species (hROS) were evaluated. Salivary concentration of SOD was significantly higher in subjects with AN compared with control group (1.010 &plusmn, 0.462 vs. 0.579 &plusmn, 0.296 U/mL, p = 0.0003). No significant differences between groups were identified for hROS (233.72 &plusmn, 88.27 vs. 199.49 &plusmn, 74.72, p = 0.15). Data from questionnaires indicated that, although most of the patients recognized the oral hygiene importance in maintaining a good oral health, more than half of them had poor oral hygiene. Altered biochemical composition of saliva in patients with AN could be interpreted as an effective defence mechanism against oxidative stress. Moreover, despite the discrepancy between clinical findings and perception of the oral health in AN population arose, the quality of life of these patients appears not to be significantly affected by their dental condition.

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.

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.

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.

Objectives: Hashimoto's thyroiditis as well as lichen planus has been associated to a number of disorders, generally of auto-immune origin. A novel possible association between oral lichen planus (OLP) and Hashimoto's thyroiditis (HT) is here proposed on the basis of a cross-sectional survey. Materials and methods: One hundred and five unrelated OLP patients were considered. Diagnosis of HT was based on positive serum anti-TPO, anti-Tg, TSH levels and the typical ultrasound pattern of the thyroid gland. Results: In the present survey, the prevalence of HT in the OLP group was 14. 3 % whereas the prevalence of HT-related hypothyroidism in the general population was reported to be equal to 1 %. By Fisher's exact test, it was revealed that the difference between our data and historical prevalence of HT was found statistically significant. Conclusion: Actually, there is no definitive hypothesis that could explain the coexistence of OLP and HT. However, considering the onset timing of HT followed by OLP in 93. 3 % of our series, we suspected a causal or predisposing role for HT. Specifically, we believe that in HT patients, circulating thyroid antibodies could contribute to trigger an organ-specific auto-immune response also in the oral mucosa or skin, leading to the development of LP lesions. Clinical relevance: Because of the large number of cases of asymptomatic chronic auto-immune thyroiditis, it would be useful that women over 40 years of age affected by OLP were screened for thyroid dysfunction, particularly HT

Objectives This study sought to assess whether transradial intervention, by minimizing access-site bleeding and vascular events, improves outcomes in patients with ST-segment elevation myocardial infarction compared with the transfemoral approach. Background Bleeding and consequent blood product transfusions have been causally associated with a higher mortality rate in patients with myocardial infarction undergoing coronary angioplasty. Methods We identified all adults undergoing percutaneous intervention for acute myocardial infarction in Emilia-Romagna, a region in the north of Italy of 4 million residents, between January 1, 2003, and July 30, 2009, at 12 referral hospitals using a region-mandated database of percutaneous coronary intervention procedures. Differences in the risk of death at 2 years between patients undergoing transfemoral versus transradial intervention, assessed on an intention-to-treat basis, were determined from vital statistics records and compared based on propensity score adjustment and matching. Results A total of 11,068 patients were treated for acute myocardial infarction (8,000 via transfemoral and 3,068 via transradial route). According to analysis of matched pairs, the 2-year, risk-adjusted mortality rates were lower for the transradial than for the transfemoral group (8.8% vs. 11.4%; p = 0.0250). The rate of vascular complications requiring surgery or need for blood transfusion were also significantly decreased in the transradial group (1.1% vs. 2.5%, p = 0.0052). Conclusions In patients undergoing angioplasty for acute myocardial infarction, transradial treatment is associated with decreased 2-year mortality rates and a reduction in the need for vascular surgery and/or blood transfusion compared with transfemoral intervention.

The presence of inflammatory reaction in peri-tumoural connective tissue is generally considered as a defense mechanism against cancer, but inflammation tissue in malignant transformation and early steps of oncogenesis has been recently proven to play a supporting and aggravating role in some carcinomas. Aims of this retrospective study were to evaluate in OSCCs the independent association of peri-tumoral inflammatory infiltrate (PTI) with local recurrence (LR) or survival outcome, and to verify whether PTI can be considered a marker of prognosis. Data from 211 cases of OSCC, only surgically treated between 1990 and 2000, were collected and retrospectively analyzed for PTI and the event LR (5 yrs follow-up at least) by means of univariate-multivariate and neural networks analyses. Patients (mean age 65.3 ± 12.4 yrs, M/F = 2.98) showed presence of PTI in 68.2% (144/211): (+) in 27.0%, (++) in 25.6%, (+++) 15.6%; PTI was found reduced in 24.7% of cases and absent in 7.1%. In overall PTI+ve group (n=144), 66 were TNM Stage I, 33 Stage II, 45 Stage III, none Stage IV. LR (mean 6 ± 4 months) was present in 87/211 (41.2%) patients, of which 43/144 (29.8%) in OSCCs with PTI [23 (+),. 13 (++) and 7 (+++)] vs. 44/67 (65.7%) in OSCC with PTI -/+ or PTI–ve ones. By univariate analysis, PTI+ve cases showed a significant lower risk to have LR (p

Objectives This study aims to evaluate whether results of “off-hours” and “regular-hours” primary angioplasty (primary percutaneous coronary intervention [pPCI]) are comparable in an unselected population of patients with ST-segment elevation acute myocardial infarction treated within a regional network organization. Background Conflicting results exist on the outcome of off-hours pPCI. Methods We analyzed in-hospital and 1-year cardiac mortality among 3,072 consecutive ST-segment elevation myocardial infarction (STEMI) patients treated with pPCI between January 1, 2004, and June 30, 2006, during regular-hours (weekdays 8:00 am to 8:00 pm ) and off-hours (weekdays 8:01 pm to 7:59 am , weekends, and holidays) within the STEMI Network of the Italian Region Emilia-Romagna (28 hospitals: 19 spoke and 9 hub interventional centers). Results Fifty-three percent of patients were treated off-hours. Baseline findings were comparable, although regular-hours patients were older and had more incidences of multivessel disease. Median pain-to-balloon (195 min, interquartile range [IQR]: 140 to 285 vs. 186 min, IQR: 130 to 280 min; p = 0.03) and door-to-balloon time (88 min, IQR: 60 to 122 vs. 77 min, IQR: 48 to 116 min; p Conclusions When pPCI is performed within an efficient STEMI network focused on reperfusion, the clinical effectiveness of either off-hours or regular-hours pPCI is comparable.

Background The long-term safety and efficacy of drug eluting stents (DES) implanted during primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) is unclear. The purpose of this study was to compare the long-term outcome of STEMI patients undergoing primary PCI with DES vs. bare metal stent (BMS) implantation. Methods In the present analysis 4764 patients were enrolled (706, 15%, received DES). We assessed the cumulative incidence of major adverse cardiac events (MACE) and stent thrombosis (ST). Results Overall, no significant difference emerged for the rates of death and reinfarction. DES implantation was associated to a reduction of target vessel revascularization (TVR) (HR 0.65, 95%CI 0.47–0.91; p =0.01), leading to a MACE reduction (HR 0.7, 95%CI 0.56–0.86; p p p =0.01). On the contrary, during the third year, adverse events tended to be higher in the DES group. ST did not differ between DES and BMS groups ( p =0.6). No differences were observed between sirolimus eluting stents and paclitaxel eluting stents. Conclusions DES implantation during primary PCI is safe and associated with a significant TVR and MACE reduction in the first two years, whereas a trend to have more adverse events in the third year is observed. More data about long-term follow-up are needed to better evaluate both safety and efficacy of DES in the setting of STEMI.

Objectives The aim of this study was to investigate whether there is a temporal pattern of ischemic events in relation to dual antiplatelet therapy in patients with unprotected left main coronary artery (ULMCA) stenosis treated with percutaneous coronary intervention (PCI). Background Identifying which periods during follow-up of patients with ULMCA stenosis treated with PCI are associated with higher risk of clinical events might help to improve therapeutic strategies. Methods We analyzed data from 15 centers involved in an observational study conducted by the Italian Society of Invasive Cardiology on patients with ULMCA stenosis treated with PCI. Eight hundred ninety-four patients were enrolled. Results At 30-day follow-up, the rate of cardiac mortality and myocardial infarction (MI) was 5.4%. In patients still taking dual antiplatelet therapy, the adjusted incidence rate ratio/10,000 patient-days of the combination of cardiac mortality and MI in the 31- to 180-day interval compared with the 181- to 360-day interval after PCI was 3.64 (p = 0.035). This risk was particularly high in patients with acute coronary syndromes. After stopping clopidogrel, the adjusted incidence rate ratio of cardiac mortality and MI in the 0- to 90-day interval compared with the 91- to 180-day interval was 4.20 (p = 0.009). Conclusions In patients with ULMCA stenosis taking dual antiplatelet therapy there is an increased hazard of cardiac mortality and MI between 31 and 180 days compared with 181 to 360 days. Furthermore, there is an increased hazard of cardiac mortality and MI in the first 90 days after stopping clopidogrel.

Percutaneous revascularization of saphenous vein grafts (SVGs) remains a challenging task. Drug-eluting stents (DESs) have been shown to decrease the incidence of restenosis in de novo native coronary artery lesions. However, their clinical value in SVGs remains to be established. We compared long-term clinical outcomes of percutaneous coronary intervention with DESs and bare metal stents (BMSs) for de novo lesions in SVGs. In a large prospective, multicenter registry, 360 patients underwent stenting of a de novo lesion in SVGs using BMSs (288 patients) or DESs (72 patients). Incidence of major adverse cardiac events (MACEs), including all-cause mortality, reinfarction, and target vessel revascularization, was recorded at a 12-month follow-up. Compared with the DES group, patients receiving BMSs were more likely to be men, to have chronic renal insufficiency or higher Charlson scores, but less likely to have undergone previous percutaneous coronary intervention. Incidence of MACEs at 12-month follow-up was similar in the 2 groups (17.8% in DES group vs 20.3% in BMS group, respectively, p = 0.460). Cox regression analysis identified age, chronic renal failure, cardiogenic shock at presentation, and ostial location of stenosis as independent predictors of long-term MACEs. In conclusion, our data suggest that rates of 12-month MACEs associated with the use of DESs and BMSs are similar in patients undergoing treatment of de novo lesions in SVGs.

We investigated expression levels of Nicotinamide N-Methyltransferase (NNMT), an enzyme involved in the biotransformation of many drugs and xenobiotic compounds, in oral squamous cell carcinoma (OSCC). Measurements were performed by semi-quantitative RT-PCR and quantitative real-time PCR in tumor and matched adjacent healthy tissue. Interestingly, NNMT was up-regulated in most of the favorable OSCCs, while no marked NNMT expression alterations between tumor and normal mucosa were detected in most of the unfavorable OSCCs. Western blot and immunohistochemical analyses also were performed and the relationship between tumor characteristics and NNMT levels in OSCC were studied to evaluate the effectiveness of NNMT as a prognostic marker in the squamous cell carcinoma of the oral cavity. In summary, the present study suggests that NNMT may have potential as a biomarker and a therapeutic target for OSCC.

Background— Epidemiology and consequences of surgery in patients with coronary stents are not clearly defined, as well as the impact of different stent types in relationship with timing of surgery. Methods and Results— Among 39 362 patients with previous coronary stenting enrolled in a multicenter prospective registry and followed for 5 years, 13 128 patients underwent 17 226 surgical procedures. The cumulative incidence of surgery at 30 days, 6 months, 1 year, and 5 years was 3.6%, 9.4%, 14.3%, and 40.0%, respectively, and of cardiac and noncardiac surgery was 0.8%, 2.1%, 2.6%, and 4.0% and 1.3%, 5.1%, 9.1%, and 31.7%, respectively. We assessed the incidence and the predictors of cardiac death, myocardial infarction, and serious bleeding event within 30 days from surgery. Cardiac death occurred in 438 patients (2.5%), myocardial infarction in 256 (1.5%), and serious bleeding event in 1099 (6.4%). Surgery increased 1.58× the risk of cardiac death during follow-up. Along with other risk factors, the interplay between stent type and time from percutaneous coronary intervention to surgery was independently associated with cardiac death/myocardial infarction. In comparison with bare-metal stent implanted >12 months before surgery, old-generation drug-eluting stent was associated with higher risk of events at any time point. Conversely, new-generation drug-eluting stent showed similar safety as bare-metal stent >12 months and between 6 and 12 months and appeared trendly safer between 0 and 6 months. Conclusions— Surgery is frequent in patients with coronary stents and carries a considerable risk of ischemic and bleeding events. Ischemic risk is inversely related with time from percutaneous coronary intervention to surgery and is influenced by stent type.

OBJECTIVES We compared the clinical outcome of sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES) in a real-world scenario. BACKGROUND In selected patients, SES has been associated with lower late luminal loss than PES. Whether this emerging biological difference could translate into different clinical efficacy in daily practice is presently unknown. METHODS This analysis included 1,676 consecutive patients with de novo coronary lesions treated solely with drug-eluting stents (SES = 992; PES = 684). All patients were enrolled in a dynamic prospective registry comprising 13 hospitals. We assessed the cumulative incidence of major adverse cardiac events (MACE), defined as death, myocardial infarction (MI), and target vessel revascularization (TVR) during follow-up. RESULTS Overall, 29% of the patients had diabetes, 23% had prior MI, and 9% had poor left ventricular function. ST-segment elevation MI was diagnosed at admission in 12%. Multivessel intervention was performed in 16%. At 1-year follow-up, SES was associated with a reduced incidence of MACE (9.2% SES vs. 14.1% PES; p = 0.007) and TVR (5.0% SES vs. 10.0% PES; p = 0.0008) compared to PES. A propensity analysis with many clinical and angiographic variables was carried out to adjust for baseline differences. In this analysis, SES was associated with a 44% risk reduction of MACE (hazard ratio 0.56, 95% confidence interval 0.39 to 0.78) and a 55% reduction of TVR (hazard ratio 0.45, 95% confidence interval 0.29 to 0.70). This result was consistent across most subgroups tested. Similar rates of death and MI were observed in the 2 treatment groups. CONCLUSIONS In this large real-world population, SES improved 1-year clinical results as compared to PES.

Coeliac disease is characterized by oral manifestations, such as dental enamel defects and recurrent oral aphthae. In this study we compared the prevalence of enamel defects and recurrent aphthous stomatitis (RAS) between patients diagnosed with coeliac disease and healthy controls.A total of 72 patients with coeliac disease were studied together with 162 normal healthy subjects as controls to individualize the prevalence of enamel defects and recurrent aphthous stomatitis (RAS) in this disease.Dental enamel defects were found in 14/70 (20\%) coeliac patients and in 9/159 (5.6\%) controls. In particular, 13/53 (24.5\%) coeliac patients with mixed or permanent dentition and 1/17 (5.8\%) coeliac children with deciduous dentition had enamel defects. Altogether, 9/145 (6.2\%) control subjects with mixed or permanent dentition had dental enamel defects. None of the controls with deciduous dentition had enamel defects. Thus, the enamel defects occurred more frequently in coeliac patients (p < 0.001). Regarding RAS, 24/72 (33.3\%) coeliac patients and 38/162 (23.4\%) control subjects had aphthous ulcers. Statistically significant differences were not observed between the two groups (p > 0.05). One in three coeliac subjects suffering from RAS received benefit from a gluten-free diet.In the present study, the prevalence of enamel defects was found to be greater in coeliac patients than healthy controls. Even though the prevalence of RAS in coeliac subjects varied from healthy controls, the difference was not statistically significant. However, more than 1/3 coeliac subjects suffering from RAS benefited from a gluten-free diet.

A series of 78 cases of oral squamous cell carcinoma was analysed by immunohistochemistry for expression of survivin, a recent apoptosis inhibitor. All cases were positive for survivin expression and were divided into two groups using a system of scores. Disease-specific survival curves were calculated according to Kaplan-Meier algorithm, and log rank test was used to compare survival curves. Then, Cox regression analysis was applied to determine the single contribution of covariates on survival rate. So, Cox analysis allowed us to detect the variables most associated to survival. Among the studied variables, such as grade of differentiation, tumor size, stage, recurrence of disease, lymph node presence, only stage and recurrence of disease were predictors of outcome; however, when we analyzed the survival without considering recurrence (that was the stronger predictor of death), a stepwise Cox analysis showed that Survivin, stage and grade of differentiation are significantly associated to survival, with a higher value for Survivin. These data suggest that survivin expression may identify cases of oral squamous cell carcinoma with more aggressive and invasive phenotype and, therefore, could influence the decision for the therapy at the time of diagnosis.

We evaluated the clinical effect of selective use of sirolimus-eluting stents (SESs) in real-world, high-risk patients. A total of 4,237 consecutive patients who underwent percutaneous coronary intervention (SES, n = 872, bare metal stents [BMSs], n = 3,365) was enrolled in a prospective regional survey. A prespecified high-risk subset of patients was selected on the basis of clinical and angiographic characteristics. A propensity score analysis was performed to compare patients who received SESs with those who received BMSs. Patients in the SES group more often had diabetes and more frequently had previous myocardial infarction or coronary revascularization, type C lesions, and multivessel procedures. Patients who presented with acute myocardial infarction were treated more often with BMSs. At 9 months, the use of SESs was associated with fewer major adverse cardiac events (death, myocardial infarction, or target lesion revascularization; hazard ratio 0.56, 95% confidence interval 0.37 to 0.85) and target lesion revascularizations (hazard ratio 0.43, 95% confidence interval 0.20 to 0.91). This decrease was more evident in a prespecified high-risk subgroup of patients (major adverse cardiac events, 8.0% SES vs 15.6% BMS, hazard ratio 0.45, 95% confidence interval 0.29 to 0.72). We conclude that selective SES use in real-world patients who have high-risk clinical and angiographic characteristics is associated with significant decreases in major adverse cardiac events and repeat revascularizations compared with BMS use.

Introduction: Survivin is a member of the Inhibitor of Apoptosis (IAP) proteins family, broadly expressed in most solid and haematological malignancies, but almost undetectable in normal adult tissues. Regarding Oral Squamous Cell Carcinoma (OSCC), Survivin expression seems to be correlated with aggressive phenotype and unfavorable outcome. In this work, the effectiveness of Survivin detection in saliva samples as diagnostic tool was investigated. Methods: 55 saliva samples from patients with histological diagnosis of OSCC and 30 samples from healthy controls matched for age and gender were collected. All samples from OSCC were collected before therapy. Saliva was analyzed using Assay Designs human Total Survivin TiterZyme® Enzyme Immunometric Assay (EIA) kit for Survivin detection and quantification. Survivin concentration (pg/ml) was studied in relationship to clinical data. Univariate statistical analysis was performed. Results: 35/55 (63.6%) among OSCC patients were found to be positive for surviving expression in saliva vs 12/30 (40%) among health controls; but the mean value was found to be higher in OSCC group (8,69 pg/ml ± 10,15 vs 2.44 pg/ml ± 4.22) reaching statistical significance (p

Background: Despite the well-known prognostic impact of systolic dysfunction in unselected patients undergoing percutaneous coronary intervention (PCI), limited data are available on its current predictive role after PCI for unprotected left main disease (ULM). We thus appraised the prognostic role of left ventricular ejection fraction (LVEF) in patients undergoing PCI for ULM with drug-eluting stents (DES). Methods: Consecutive eligible subjects were retrospectively enrolled in a national registry. Patients were divided into three groups: LVEF < 30%, LVEF 30-45%, and LVEF > 45%. Relevant baseline and outcome data were compared with bivariate and multivariable tests. Results: A total of 975 subjects was included (LVEF < 30%: 46, LVEF 30-45%: 208, LVEF > 45%: 721). Patients with LVEF < 30% had several other unfavorable clinical features, including older age and higher EuroSCORE. Adverse event rates were different already at 7 days (p = 0.012 for all-cause death and p = 0.015 for major adverse cardiac events [MACE]), with even more significant trends up to 30 days and at long-term (p < 0.001 for death, and p < 0.001 for MACE). After a median of 18 months, risk of death totaled 39 versus 13 versus 8% (p < 0.001) and risk of MACE 44 versus 24 versus 22% (p = 0.003). Multivariable analyses showed however that reduced LVEF was not an independent predictor of adverse events at any time-point. Conclusions: Whereas reduced LVEF is apparently a significant predictor of adverse events after PCI with DES for ULM, its prognostic impact is mostly due to clustering with other adverse feature

Aims: Percutaneous coronary intervention (PCI) is increasingly being used for unprotected left main (ULM) disease. Limited data are available on sex-related differences in this setting. We investigated gender-associated differences in patients undergoing stent-based PCI for ULM. Methods and results: We analysed baseline, procedural and long-term data of patients with ULM undergoing stent-based PCI at participating centres. The primary end-point was the long-term rate of major cardiovascular events rate (MACE, i.e., the composite of death, myocardial infarction, or target lesion revascularisation). The study population included 1,452 cases, with 27.8% females and 72.2% males. Women were older, more frequently diabetic, hypertensive or presenting with an acute coronary syndrome, and thus with a higher EuroSCORE, but were less commonly treated with drug-eluting stents (DES), in comparison to men (all p

In 20 patients with recurrent episodes of lone paroxysmal atrial fibrillation we assessed the onset pattern of each episode of either atrial fibrillation or of atrial flutter during a 24-h Holter monitoring. We evaluated 24 twenty-four-hour Holter tape recordings and our data are related to 168 episodes of paroxysmal atrial fibrillation and 27 episodes of paroxysmal atrial flutter. Eighty-five percent of atrial fibrillations and 67% of atrial flutters were of short duration (less than 5 min). The majority of patients (80%) had either nocturnal or daily episodes of arrhythmia and PP intervals immediately before onset of arrhythmia did not show significant variations in 77% of cases. The coupling interval of the supraventricular premature beats eliciting atrial fibrillation was significantly shorter than the coupling intervals of the spontaneous isolated supraventricular premature beats (p less than 0.0001); again, in 6 patients with either atrial fibrillation or flutter, the coupling interval at onset of fibrillation was significantly shorter in comparison to flutter (p less than 0.0001). In conclusion, vagal or sympathetic prevalence does not seem to influence significantly the beginning of the arrhythmia, while the coupling interval of the atrial premature beats plays a critical role in the inducibility of atrial flutter or fibrillation.

Craniofacial morphology of patients with nevoid basal cell carcinoma syndrome (NBCCS) has sometimes been reported at clinical examination, but any investigation has described it on the basis of cephalometric measurements.The purpose of this study was to conduct a cephalometric analysis of patients with NBCCS and to compare measurements with non-NBCCS subjects of similar ages, to elucidate if there is any relationship between NBCCS and craniofacial morphology.The study population consisted of 14 adult patients (9 men and 5 women), ranging in age from 18.2 to 56.8 years, with the diagnosis of NBCCS, with good-quality lateral cephalometric radiographs, and 14 adult healthy patients matched for age and sex to the NBCCS group. Cephalometric measurements were carried out on radiographs, and measurements of angles and distances were performed.Statistical differences between NBCCS subjects and controls were observed. Data analysis displayed that the measurements of the anterior cranial base (P

Data are limited about the relative efficacy of drug-eluting stents (DESs) versus bare-metal stents (BMSs) for the treatment of unprotected left main coronary artery (ULMCA) stenosis. The survey promoted by the Italian Society of Invasive Cardiology on ULMCA stenosis was an observational study involving 19 high-volume Italian centers of patients with ULMCA stenosis treated using percutaneous coronary intervention (PCI). From January 2002 to December 2006, of 1,453 patients identified with ULMCA stenosis treated with PCI, 1,111 were treated with DESs and 342 were treated with BMSs. During a 2-year follow-up, risk-adjusted survival free from cardiac death was significantly higher in patients treated with DESs than in those treated with BMSs. The propensity-adjusted hazard ratio for risk of 2-year cardiac mortality after DES versus BMS implantation was 0.49 (95% confidence interval 0.32 to 0.77). The benefit of DESs in reducing cardiac mortality was obtained in the period from 3 to 6 months and maintained up to 2 years. In conclusion, for patients with ULMCA stenosis undergoing PCI, DES implantation was associated with higher adjusted rates of 2-year survival free from cardiac death. The benefit of DESs in reducing cardiac mortality was obtained in the period in which clinical manifestations of restenosis usually peak.

Aims In this study, we compared the clinical outcomes of elderly patients with unprotected left main coronary artery (ULMCA) stenosis treated with either coronary artery bypass grafting (CABG) or drug-eluting stent (DES). Methods and results From January 2003 to April 2006, 259 patients with ULMCA stenosis and age ≥75 years underwent coronary revascularization with either CABG or DES. One hundred and sixty-one patients were treated with CABG and 98 with DES. The cumulative unadjusted rates of 2-year mortality were 17% in CABG-treated patients and 18% in those treated with DES ( P = 0.71). The adjusted rates of 2-year survival were 85% for CABG-treated patients and 87% for DES-treated patients ( P = 0.74). The incidence of 2-year myocardial infarction was 6% in CABG-treated patients and 4% in DES-treated patients ( P = 0.11). The incidence of target lesion revascularization (TLR) was 3% in CABG-treated patients and 25% in DES-treated patients ( P < 0.0001). In the multivariable analysis, peripheral vascular disease, left ventricular ejection fraction and acute coronary syndrome were independent predictors of 2-year mortality. Conclusion In this study, we could not demonstrate a difference in mortality between CABG-treated patients and those treated with DES. However, the rate of TLR was higher in the DES group.

p63 belongs to a protein family that includes 2 structurally related proteins, p53 and p73. The aim of this study was to investigate the biologic role of p63 in oral tumorigenesis and its possible role as prognostic marker in oral cancer. Ninety-four cases of oral squamous cell carcinoma and 10 cases of normal mucosa were analyzed for p63 expression by immunohistochemistry. Normal oral mucosa showed a basal and parabasal expression of p63. Five (5.3%) cases of oral cancer showed less than 10% of positive tumor cells; in 33 (35.1%) cases the positive tumor cells comprised between 10% and less than 30%, in 36 (38.3%) cases the positive tumor cells comprised between 30% and less than 50%, and in 20 (21.3%) cases the positive tumor cells were more than 50%. There was also a statistically significant correlation between p63 expression and tumor differentiation: p63 expression was amplified in poorly differentiated tumors (P < .05). When analyzed for prognostic significance, patients with perineural infiltration had poorer survival rates than the group with no perineural infiltration (P < .05) and patients with increased p63 expression had poorer survival rates than the group with reduced p63 expression (P < .05). The statistical analysis showed no significant correlation between p63 expression, sex, age, tumor size, staging, recurrence, and metastasis. Cases with diffuse p63 expression were more aggressive and poorly differentiated and related to a poorer prognosis. These data suggest that p63 expression may be useful to identify cases of oral squamous cell carcinoma with more aggressive and invasive phenotype providing novel diagnostic and prognostic information on individual patient survival with oral cancers.

Tako-tsubo syndrome is a clinical entity of transient left ventricular apical ballooning, frequently precipitated by a stressful event. The syndrome can be complicated by left ventricular outflow tract (LVOT) obstruction and can be recurrent. Herewe describe a case of a 64 years old female who had two episodes of tako-tsubo syndrome characterized by a similar stressful event and similar clinical and instrumental characteristics. Apical ballooning syndrome (or Tako-tsubo cardiomyopathy) is a clinical entity characterized by acute but rapidly reversible left ventricular (LV) systolic dysfunction. Recurrence of Tako-stubo syndrome is not frequent as well as LVOT obstruction, mitral regurgitation and shock. We describe a case of recurrent tako-tsubo cardiomyopathy with recurrence of LVOT obstruction and mitral regurgitation and complicated by cardiogenic shock. A 64 years old female with hypertension and chronic obstructive pulmonary disease (COPD) was admitted to the hospital in June 2005 with an acute recurrent chest pain. The patient was on cortisone from 24 h before because of an asthma exacerbation and she reported having also vomit and fright. The clinical symptom started in the morning but she had the first medical contact only in the evening. At the admission in intensive care unit (ICU) the patients was asymptomatic, the electrocardiogram (ECG) showed a 1.5 mm ST elevation from V3 to V6, DI, DII and aVL. Systolic blood pressure was 90 mm Hg, and an echocardiography exam showed an apical ballooning of the left ventricle with moderate mitral regurgitation secondary to left ventricular outflow tract (LVOT) obstruction (Fig. 1). Promptly, glycoprotein inhibitors and heparine were started and coronary angiography was performed the day after. Ventriculography confirmed the apical ballooning and normal coronary artery. Left ventricular ejection fraction (LVEF) was 35% (Fig. 2). The peak of plasma MB-creatinine kinase and of troponin I was 28.5 ng/mL and 6.9 ng/mL respectively. The systolic pressure remained stable at 90 mm Hg for four days with gradually recover until 110 mm Hg. The patient had no signs of congestive heart failure and was discharged after six days. Complete normalization of LVEF was documented at the follow-up. In December 2009 the woman was admitted in hospital for an exacerbation of her COPD. She was treated for eight days with cortisone, ipratropium, salmeterol and antibiotics with a good clinical response. During her stay she presented chest pain and the ECG showed a 2.5 mm STelevation fromV3 to V6, DI and aVL. The coronary angiography showed no obstructive coronary lesions and an apical ballooning aspect at the ventriculogram (Fig. 3). In ICU the patient developed a cardiogenic shock (initial systolic blood pressure of 90 mm Hg with rapid deterioration until 60 mm Hg). An urgent echocardiogram showed the apical ballooning with the concomitance of LVOT obstruction, systolic anterior motion of mitral valve and severe mitral regurgitation (Figs. 3 and 4). Peak dynamic intraventricular pressure gradient detected by echocardiography was 80 mm Hg. The LVEF was 25%. Urgently an intra-aortic balloon pump (IABP) was placed and then she was treated with low-dose beta-blockers until restoration of good pressure and initial recovery of LVEF. After a period of seven days the IABP was removed: the LVEF was 35% and the peak dynamic pressure gradient was lower (12 mm Hg). The peak of plasma MB-creatinine kinase and troponin T was 18.07 μg/L and 0.55 μg/L respectively. She was discharged after other eight days with a good pressure, no sign of congestive heart failure, a LVEF of 48% and absence of sign of LVOT obstruction and mitral regurgitation. Normalization of LVEF was after documented. Tako-tsubo syndrome, which is also called stress cardiomyopathy or transient left ventricular apical ballooning syndrome, is a clinical entity frequently precipitated by a stressful event. Initially, the syndrome was described in Japanese and afterwards an increasing number of cases has been reported also in Caucasian [1,2]. The main features are the absence of coronary atherosclerosis disease and the reversibility of left ventricular dysfunction. Recurrence of Tako-tsubo syndrome is not frequent. The yearly recurrence rate is 2.9% over the first few years, subsequently decreasing to 1.3% per year [3,4]. The syndrome can be also complicated by LVOT obstruction as previously described [5]. The report described is a rare case of recurrent Tako-Tsubo syndrome with recurrence of similar clinical and instrumental signs. In both episodes the main common findings were hypotension and an echocardiographic aspect of LVOT obstruction, systolic anterior motion and secondary mitral regurgitation. The recurrent episode was much more severe with a cardiogenic shock requiring the IABP positioning. Furthermore the patients experienced in both cases the same physical stressful event.

Delay in diagnosing oral squamous cell carcinoma (OSCC) can be still identified as a major cause of its high morbidity and mortality. To date, the early diagnosis for OSCC is mainly based on clinical oral examination and there is an urgent need for reliable markers; thus, advancements in molecular technologies has set the stage for investigating new markers, as well as new diagnostic matrices. The aim of the present study is to investigate the presence of proteomic signatures of OSCC in saliva and their use as potential biomarkers for early and non-invasive diagnosis. Saliva from 45 OSCC patients and 30 healthy controls was analysed by SELDI-TOF mass spectrometry and ProteinChip® technology. A supervised multivariate statistical analysis (Classification and Regression Tree - CART) was used to build models for discriminating between OSCC and controls, and between early (ES-OSCC) and late stage (LS-OSCC) cancers. The peptide with 8041 Da mass was 22-fold more expressed in OSCC, thus being a suitable potential biomarker. Classification and regression analysis allowed to build a model that was capable of correctly classifying all cancers and controls in an independent testing set, using the 8041 m/z peak as splitter. Eleven peaks were also differently expressed between ES-OSCCand LS-OSCC, but, basing on these differences, it was not possible to build an algorithm to predict tumour staging. These findings confirm that saliva proteome in OSCC patients is different from healthy controls and these variations might reflect different stages of disease progression and are worthy of further validation as diagnostic and prognostic biomarkers.