Prevalence of retained/transmigrated permanent and persistence of primary teeth associated with odontomas in young children.

AIM: Odontomas are odontogenic tumours of the jaws; they are generally asymptomatic with an unknown aetiology. This study was conducted on non-syndromic children aged 9 to 14 years to explore the side effects deriving from the presence of these benign tumours, as retention, transmigration, ectopic eruption of permanent teeth and the permanence of primary teeth in the affected area. METHODS: Two hundred panoramic (OPT) and 92 Cone Beam Computed Tomography radiographs (CBCT) of patients (130 males and 70 females) were analysed from February 2018 to December 2019. Two hundred odontomas (145 compound and 55 complex type) and 800 teeth (160 primary and 640 permanent) were included. RESULTS: The prevalence of these tumours in both male and female subjects was 65% and 35%, respectively; the prevalence of compound odontomas in maxillary and mandibular bones was respectively 27.58% and 72.41%. The prevalence of complex odontomas in maxillary bones in female and male subjects was 37.5% and 62.5% respectively. It was observed the presence of a primary tooth in 81% of cases, the presence of retained teeth in 16.5% and a dental transmigration in the remaining 2.5% of cases in the compound type. Gender (p?=0.158) has no significant correlation. CONCLUSIONS: An early diagnosis and removal of odontomas in primary dentition is crucial in order to prevent later dental complications. Since the detection of odontomas is mainly an accidental radiological finding, the need for routine radiographic analysis should be highlighted.

Will a tumor pandemic come after the COVID-19 pandemic? Head and Neck cancer perspective.

The COVID-19 pandemic demands a reassessment of head and neck oncology treatment paradigms by posing several challenges for oncology services, with unprecedented pressure on the regional health care system. Since February 2020 this has severely disrupted health-care services, leading to accumulating clinic caseload and substantial delays for operations. The head and neck cancer services have been faced with the difficult task of managing the balance between infection risk to health-care providers and the risk of disease progression from prolonged waiting times. Herein, we share our experience in Firenze (Italy) and propose our action plan on the management of head and neck cancer services via multi-institution collaboration.

The surgical treatment of unilateral vocal cord paralysis (UVCP): qualitative review analysis and meta-analysis study.

PURPOSE: The objectives of this meta-analysis were to summarize the key surgical procedures for UVCP and to evaluate which of these is associated with better results in terms of vocal improvement. METHODS: A systematic review of the literature was conducted in search of articles focused on the comparison of voice outcome between different techniques for the UVCP treatment. Then, a quantitative analysis was carried out for papers published from 2013 onwards, reporting only adult patients with unilateral paralysis for each study, and each surgical technique was evaluated for its capability of achieving good functional outcomes in terms of GRBAS-I scale and maximum phonation time in seconds (MPT). RESULTS: The search identified 1853 publications. A total of 159 articles were stratified and included according to our selection criteria. 21 out of 159 articles were selected for quantitative synthesis. For trans-oral techniques: the mean GRBAS-I scale were 2.33 before injection and 0.41 after injection. The mean MPT before injection were 4.78 and 12.50 after injection. For open techniques the mean GRBAS-I scale were 2.43 before surgery and 0.68 after surgery. For open technique, the mean MPT were 3.50 before surgery and 12.40 after surgery. CONCLUSIONS: The two types of techniques lead to an improvement in terms of vocal outcomes emphasizing that from the examined literature an indication emerges to perform an early injection because this could reduce the possible need for a more invasive intervention of permanent medialization in the future.

A STAT4 variant increases liver fibrosis risk in Caucasian patients with chronic hepatitis B.

BACKGROUND: Host genetic modifiers of the natural history of chronic hepatitis B (CHB) remain poorly understood. Recently, a genome-wide association study (GWAS)-identified polymorphism in the STAT4 gene that contributes to the risk for hepatocellular carcinoma (HCC) was shown to be associated with the full spectrum of hepatitis B virus (HBV) outcomes in Asian patients. However, the functional mechanisms for this effect are unknown and the role of the variant in modulating HBV disease in Caucasians has not been investigated. AIMS: To determine whether STAT4 genetic variation is associated with liver injury in Caucasian patients with CHB and to investigate potential mechanisms mediating this effect. METHODS: STAT4 rs7574865 was genotyped in 1085 subjects (830 with CHB and 255 healthy controls). STAT4 expression in liver, PBMCs and NK cells, STAT4 phosphorylation and secretion of interferon-gamma (IFN-γ) according to STAT4 genetic variation was examined. RESULTS: STAT4 rs7574865 genotype was independently associated with hepatic inflammation (OR: 1.42, 95% CI: 1.07-2.06, P = 0.02) and advanced fibrosis (OR: 1.83, 95% CI: 1.19-2.83, P = 0.006). The minor allele frequency of rs7574865 was significantly lower than that in healthy controls. rs7574865 GG risk carriers expressed lower levels of STAT4 in liver, PBMCs and in NK cells, while NK cells from patients with the risk genotype had impaired STAT4 phosphorylation following stimulation with IL-12/IL-18 and a reduction in secretion of IFN-γ. CONCLUSION: Genetic susceptibility to HBV persistence, hepatic inflammation and fibrosis in Caucasians associates with STAT4 rs7574865 variant. Downstream effects on NK cell function through STAT4 phosphorylation-dependent IFN-γ production likely contribute to these effects.

Colonization of Legionella spp. In dental unit waterlines.

Legionella spp. are ubiquitous in aquatic habitats and water distribution systems, including dental unit waterlines. Surveys have shown that the percentage of samples taken at different dental sites that were positive for Legionella spp. were highly variable and ranged from 0% to 100%. Cultivation is the principal approach to evaluating bacterial contamination employed in the past, but applying this approach to testing for Legionella spp. may result in false-negative data or underestimated bacterial counts. PCR and direct fluorescent counts can detect viable non-cultivable bacteria, which are not counted by plating procedures. Legionella spp., commonly form such viable non-culturable cells and it is likely that they contribute to the difference between plate count results and those of PCR and fluorescent-antibody detection. However, studies have shown that Legionella is present in the municipal water source in spite of the current filtration and chlorination procedures. Once Legionella reaches the building water system, it settles down into a biofilm layer of stagnant water. By means of this layer, Legionella can protect itself from antimicrobial agents and then multiply. Dental unit waterlines may be contaminated with opportunistic bacteria. The water quality in the dental units should be controlled to eliminate opportunistic pathogens and to provide water for dental treatment that meets public health standards for potable water.

Focus on periodontal disease and development of endocarditis.

Infective endocarditis is a devastating disease with high morbidity and mortality. The link to oral bacteria has been known for many decades and has caused ongoing concern for dentists, patients and cardiologists. The microbiota of the mouth is extremely diverse and more than 700 bacterial species have been detected. Half of them are uncultivable so far. Oral microbiota is not uniform, specific sites exist in the mouth such as tongue, palate, cheek, teeth and periodontal pockets that have their own microbiota. Factors involved in the development of a bacterial endocarditis are difficult to define but a vulnerable surface (i.e. a damaged endocardium) and a high bacterial load in the blood seems to be decisive. The cause of microorganisms, in 90% of cases, are staphylococcus, streptococcus and enterococcus. Oral streptococci belong to viridans group (streptococcus mutans and streptococcus sanguis). As they are part of dental plaque, they could enter the bloodstream causing bacteraemia through daily habits like chewing or tooth brushing. Effective treatment of periodontal infections is important to reduce local inflammation and bacteraemia. In addition, poor periodontal health appears to increase the risk of cardiovascular disease, pulmonary disease, and preterm and low birth weight. CONCLUSIONS: Long-standing oral disease prevention protocols reduce the risk of developing periodontal disease. Data suggests that methods used to prevent cases of IE that originate from oral bacteria should focus on improving oral hygiene and reducing or eliminating gingivitis, which should reduce the incidence of bacteraemia after tooth-brushing and the need to extract teeth owing to periodontal disease and caries.

Radiosurgery-assisted gingival displacement: a proof of concept technique to enhance the efficiency of intraoral digital impression.

Nowadays, an increasing number of dentists are using intraoral scanners (IOS) in their daily practice as an alternative to conventional impression taking. One of the main concerns is related to the capability of scanning the subgingival anatomy of the die, usually very challenging due to the limited operative field and the presence of oral fluids. The radiosurgery assisted gingival displacement technique (RAGD) may enhance the intraoral optical scanning of the finish line and neighbor tooth anatomy. The contour of the interim prosthesis is used to drive the tip of radiosurgery electrode along the tooth surface and open selectively the gingival crevice with a prosthetically-driven and minimally invasive approach. The clinical implication of this technique is related to increasing the efficiency and accuracy of the digital impression technique in the critical zone of the prosthetic shoulder.

How to avoid life-threatening complications following head and neck space infections: an algorithm-based approach to apply during times of emergency. When and why to hospitalise a neck infection patient.

BACKGROUND: Head and neck space infections present with a potential mortality rate of 40-50 per cent. This paper proposes an algorithm-based management of head and neck space infection to prevent life-threatening events. METHODS: A total of 225 patients with head and neck space infection were prospectively analysed at our institution. An experimental scoring system determined the level of clinical risk for the development of major complications. Accordingly, patients were classified into three risk groups: low-, intermediate- and high-risk. RESULTS: Only intermediate- and high-risk patients were hospitalised. Intermediate-risk patients received intravenous medical therapy with daily re-evaluation; 18 of them required delayed surgery. Of the high-risk patients, three required immediate surgical treatment and five received delayed surgery, while in five cases medical therapy was the only treatment received. Low-risk patients were treated in an out-patient setting. CONCLUSION: The algorithm-based management of head and neck space infection was successful in enabling the avoidance of lethal complications onset.

Adipocytes sustain pancreatic cancer progression through a non-canonical WNT paracrine network inducing ROR2 nuclear shuttling.

BACKGROUND: Solid epidemiological evidences connect obesity with incidence, stage and survival in pancreatic cancer. However, the underlying mechanistic basis linking adipocytes to pancreatic cancer progression remain largely elusive. We hypothesized that factors secreted by adipocytes could be responsible for epithelial-to-mesenchymal transition (EMT) induction and, in turn, a more aggressive phenotype in models of pancreatic preneoplastic lesions. METHODS: We studied the role of factors secreted by two adipogenic model systems from primary human bone marrow stromal cells (hBMSCs) in an in vitro experimental cell transformation model system of human pancreatic ductal epithelial (HPDE) cell stably expressing activated KRAS (HPDE/KRAS),Results:We measured a significant induction of EMT and aggressiveness in HPDE and HPDE/KRAS cell lines when cultured with medium conditioned by fully differentiated adipocytes (ADIPOCM) if compared with the same cells cultured with medium conditioned by hBMSC (hBMSCCM) from two different healthy donors. Several genes coding for soluble modulators of the non-canonical WNT signaling pathway, including FRZB, SFRP2, RSPO1, WNT5A and 5B were significantly overexpressed in fully differentiated adipocytes than in their respective in hBMSC. ADIPOCM induced the overexpression and the nuclear translocation of the Frizzled family member receptor tyrosine kinase-like orphan receptor (Ror) 2 in HPDE and HPDE/KRAS cells. Vantictumab, an anti-Frizzled monoclonal antibody, reduced ROR2 nuclear translocation and in turn the EMT and aggressiveness in HPDE and HPDE/KRAS cells. CONCLUSIONS: We demonstrated that adipocytes could induce EMT and aggressiveness in models of pancreatic preneoplastic lesions by orchestrating a complex paracrine signaling of soluble modulators of the non-canonical WNT signaling pathway that determine, in turn, the activation and nuclear translocation of ROR2. This signaling pathway could represent a novel target for pancreatic cancer chemoprevention. Most importantly, these factors could serve as novel biomarkers to select a risk population among obese subjects for screening and, thus, early diagnosis of pancreatic cancer.

Randomised clinical trial: sofosbuvir and ledipasvir in patients with transfusion-dependent thalassaemia and HCV genotype 1 or 4 infection.

BACKGROUND: Patients with thalassaemia major depend on blood transfusions. In Italy, up to 80% of thalassaemia patients bear HCV antibodies due to HCV contaminated transfusions before 1990. Thalassaemia patients with HCV infection have high risk of developing HCC. Treatment based on Pegylated-IFN (Peg-IFN) and Ribavirin (RBV) was limited by relevant side effects. AIM: To evaluate the impact of Sofosbuvir/Ledipasvir (SOF/LDV) fixed dose combination for 12 weeks without RBV, in patients with thalassaemia major and HCV Genotype 1 or 4 (GT1/4). METHODS: Open label, historically-controlled, nationwide multicentre study in thalassaemia patients including naïve with cirrhosis and prior treatment failure without cirrhosis. SOF/LDV single pill was administered for 12 weeks to 100 patients of whom 16% had cirrhosis. The control group included 96 patients with comparable baseline characteristics treated with Peg-IFN/RBV. The primary end point was sustained virologic response at follow-up week 12 or 24 after IFN-free or Peg-IFN/RBV, respectively. RESULTS: In the study group, sustained virological response (SVR) was reported in 98% of patients (95% CI 95.3%-100%). Cirrhotic as well as prior treatment failure achieved 100% SVR. In the control group, SVR was 47.9% (95% CI 37.9%-57.9%). Adverse events including fatigue, headache, nausea, decrease in haemoglobin or increase in ferritin levels were rare and significantly less common in the study than in the historical control group. CONCLUSIONS: In conclusion, SOF/LDV for 12 weeks provides simple, highly effective and safe Peg-IFN/RBV-free treatment for HCV GT1/4 thalassaemia patients. EUDRACT number 2015-002401-1.

Streamlined bioreactor-based production of human cartilage tissues.

Engineered tissue grafts have been manufactured using methods based predominantly on traditional labour-intensive manual benchtop techniques. These methods impart significant regulatory and economic challenges, hindering the successful translation of engineered tissue products to the clinic. Alternatively, bioreactor-based production systems have the potential to overcome such limitations. In this work, we present an innovative manufacturing approach to engineer cartilage tissue within a single bioreactor system, starting from freshly isolated human primary chondrocytes, through the generation of cartilaginous tissue grafts. The limited number of primary chondrocytes that can be isolated from a small clinically-sized cartilage biopsy could be seeded and extensively expanded directly within a 3D scaffold in our perfusion bioreactor (5.4 ± 0.9 doublings in 2 weeks), bypassing conventional 2D expansion in flasks. Chondrocytes expanded in 3D scaffolds better maintained a chondrogenic phenotype than chondrocytes expanded on plastic flasks (collagen type II mRNA, 18-fold; Sox-9, 11-fold). After this "3D expansion" phase, bioreactor culture conditions were changed to subsequently support chondrogenic differentiation for two weeks. Engineered tissues based on 3D-expanded chondrocytes were more cartilaginous than tissues generated from chondrocytes previously expanded in flasks. We then demonstrated that this streamlined bioreactor-based process could be adapted to effectively generate up-scaled cartilage grafts in a size with clinical relevance (50 mm diameter). Streamlined and robust tissue engineering processes, as the one described here, may be key for the future manufacturing of grafts for clinical applications, as they facilitate the establishment of compact and closed bioreactor-based production systems, with minimal automation requirements, lower operating costs, and increased compliance to regulatory guidelines.

Liver Transplantation and Abuse of Drugs and Alcohol: A Correlation Between Scales of the MMPI-2.

BACKGROUND: Clinical practice requires an accurate psychological assessment of subjects with clinical history of alcohol abuse and/or substance abuse (abuse history [AH]) for therapeutic choice. This study aims to identify significant correlations between the Minnesota Multiphasic Personality Inventory (MMPI)-2 scales in patients awaiting liver transplantation. METHODS: We evaluated a personality questionnaire containing MMPI-2 scales in the sample of 308 patients (81.8% males and 18.2% females) awaiting liver transplantation. The AH group composed 44.49% of patients and in the abuse free (AF) group, 55.51%. Scales were compared using Shapiro-Wilk test and Mann-Whitney U test. Interrelationships were examined using Spearman's correlation. RESULTS: This analysis found 27 scales of the MMPI-2 that were statistically different between 2 groups (AF and AH). In the AH group, we found a significant correlation between the following pairs of scales: Schizophrenia Scale (Sc) with the Addictions Potential Scale, Social Introversion scale (Si) with the Psychopathic Deviate scale (Pd), and Social Discomfort scale with Pd; the ES scale was negatively correlated with the Sc and Si scales. This interim study showed that the understanding of these indicators is crucial both for the assessment accuracy and for a prediction of the degree of therapy compliance after the transplantation. CONCLUSIONS: The scales of the MMPI-2 indicated a marked tendency to emotional rigidity, a lack of self-esteem and susceptibility judgment. Social introversion and social discomfort trends lead to impulsive behavior and deviant actions that combine poorly with good compliance with treatment.

Olfactory event-related potentials: a new approach for the evaluation of olfaction in nasopharyngeal carcinoma patients treated with chemo-radiotherapy.

OBJECTIVE: Olfactory dysfunction is a possible side effect of chemo-radiotherapy performed in patients affected by nasopharyngeal carcinoma. Self-rating measurements and olfactory event-related potentials were used and compared in order to evaluate the impact of this treatment on the olfactory system. METHODS: Nine patients underwent subjective evaluation of olfactory function (using visual analogue scales for olfactory symptoms and quality of life, and a six-item Hyposmia Rating Scale), and a quantitative and objective measurement (olfactory event-related potentials). RESULTS: Spearman's rank correlation analyses highlighted significant relationships between the clinical scales and olfactory event-related potentials. Inter-group analyses showed significant differences in the latency and in the amplitude of olfactory event-related potentials between patients and controls. CONCLUSION: Taking into account the small sample size and the lack of pre-treatment assessment, olfactory event-related potentials seemed to allow a more objective diagnosis of unilateral and bilateral olfactory loss. Moreover, olfactory event-related potentials and subjective scales results were concordant.

TAK1-regulated expression of BIRC3 predicts resistance to preoperative chemoradiotherapy in oesophageal adenocarcinoma patients.

BACKGROUND: About 20% of resectable oesophageal carcinoma is resistant to preoperative chemoradiotherapy. Here we hypothesised that the expression of the antiapoptotic gene Baculoviral inhibitor of apoptosis repeat containing (BIRC)3 induced by the transforming growth factor ß activated kinase 1 (TAK1) might be responsible for the resistance to the proapoptotic effect of chemoradiotherapy in oesophageal carcinoma. METHODS: TAK1 kinase activity was inhibited in FLO-1 and KYAE-1 oesophageal adenocarcinoma cells using (5Z)-7-oxozeaenol. The BIRC3 mRNA expression was measured by qRT-PCR in 65 pretreatment frozen biopsies from patients receiving preoperatively docetaxel, cisplatin, 5-fluorouracil, and concurrent radiotherapy. Receiver operator characteristic (ROC) analyses were performed to determine the performance of BIRC3 expression levels in distinguishing patients with sensitive or resistant carcinoma. RESULTS: In vitro, (5Z)-7-oxozeaenol significantly reduced BIRC3 expression in FLO-1 and KYAE-1 cells. Exposure to chemotherapeutic agents or radiotherapy plus (5Z)-7-oxozeaenol resulted in a strong synergistic antiapoptotic effect. In patients, median expression of BIRC3 was significantly (P<0.0001) higher in adenocarcinoma than in the more sensitive squamous cell carcinoma subtype. The BIRC3 expression significantly discriminated patients with sensitive or resistant adenocarcinoma (AUC-ROC=0.7773 and 0.8074 by size-based pathological response or Mandard's tumour regression grade classifications, respectively). CONCLUSIONS: The BIRC3 expression might be a valid biomarker for predicting patients with oesophageal adenocarcinoma that could most likely benefit from preoperative chemoradiotherapy.

Safety of vitamin K antagonist treatment for splanchnic vein thrombosis: a multicenter cohort study.

BACKGROUND: The treatment of splanchnic vein thrombosis (SVT) is challenging, due to the increased risk of bleeding and potentially life-threatening complications. Current recommendations are based on evidence from the treatment of venous thrombosis in usual sites, but small observational studies in SVT population suggest that the bleeding risk may offset the benefit of anticoagulant treatment in this setting. The aim of this study was to evaluate the safety of vitamin K antagonists (VKAs) in SVT patients. METHODS: We retrospectively included SVT patients treated with VKAs followed by 37 Italian anticoagulation clinics, until June 2013. The primary outcome was the incidence of major bleeding (MB), according to the ISTH definition, during VKA treatment. Vascular events, including both arterial and venous thrombosis, and mortality were also documented. RESULTS: Three hundred and seventy-five patients were included (median age 53 years; 54.7% males). During a median VKA treatment duration of 1.98 years, 15 MB events occurred, corresponding to an incidence rate of 1.24 (95% confidence interval [CI], 0.75-2.06) per 100 patient-years. Gastrointestinal bleeding represented 40% of all MB events. At multivariate analysis, the presence of esophageal varices emerged as independent predictor of MB (hazard ratio 5.4; 95% CI, 1.4-21.1). The incidence rate of vascular events on treatment was 1.37 (95% CI, 0.84-2.23) per 100 patient-years and the mortality rate was 0.83 (95% CI, 0.44-1.54) per 100 patient-years. CONCLUSIONS: Selected SVT patients followed by anticoagulation clinics for the management of VKA treatment show a low rate of major bleeding and vascular events.

Potential use of acupuncture in the treatment of first bite syndrome.

OBJECTIVES: First bite syndrome (FBS) is an early postoperative pain syndrome characterized by the sudden onset of pain in the parotid region at the first bite of each meal. The etiology is not certain, hence a standardized therapy does not exist. METHODS: A 50-year old woman referred to us complaining of a swelling in the right parotid region. Fine-needle aspiration biopsy (FNAB) was diagnostic for pleomorphus adenoma of the deep lobe of the parotid gland. A 50-year old man presented with a mass in the right side of the neck, FNAB was diagnostic for parapharyngeal space neurinoma. The first patient was submitted to total parotidectomy with facial nerve preservation, the second to extracapsular dissection of the tumor. A week after surgery both patients developed FBS. A qualitative/quantitative description of pain was obtained by means of a self-coded questionnaire. The score ranges from 8 to 44, corresponding to the lowest and the highest discomfort possible, respectively. Acupuncture was used to treat these 2 patients. The treatment protocol comprised 6 sessions, one per week, lasting 30 minutes each. RESULTS: Our questionnaire was administered before and after treatment and the score dropped from 33 to 25 in the female, from 30 to 15 in the male patient. CONCLUSION: FBS is a complication of upper cervical surgery with a high morbidity rate. We describe the first two cases of FBS that were successfully treated with acupuncture in our ENT department. We believe that this procedure may represent a valid therapeutic alternative in the future.