Aseptic Meningitis in Oral Medicine: Exploring the Key Elements for a Challenging Diagnosis: A Review of the Literature and Two Case Reports

Aseptic meningitis (AM) is a potentially severe and life-threatening disease characterized by meningeal inflammation, usually with mononuclear pleocytosis. It represents a challenging and controversial issue in medicine for multiple etiologies, classification, and difficult diagnosis in the face of nonspecific sets of signs and symptoms. In the area of interest of oral medicine, in specific clusters of patients, even if rare, the occurrence of aseptic meningitis can pose a diagnostic and management dilemma in the following potential etiologies: (i) systemic diseases with oral and meningeal involvement, which include Behçet’s disease and Sjögren syndrome; (ii) drug-induced aseptic meningitis; (iii) aseptic viral meningitis, mostly related to herpes simplex virus infection and hand, foot, and mouth disease, caused by enteroviruses. In this review, clinical manifestations, diagnostic methodologies, incidence, treatment, and prognosis for each of these clinical entities are provided. Furthermore, two illustrative case reports are described: a patient suffering from recurrent oral ulcers, in which a sudden onset of AM allows us to diagnose Neuro Behçet’s disease, and a patient affected by pemphigus vulgaris, manifesting a drug-induced AM. Exploring this complex clinical entity scenario, it is clear that an oral medicine specialist has a place on any multidisciplinary team in making such a challenging diagnosis

Human Papilloma Virus Vaccination and Oropharyngeal Cancer: Knowledge, Perception and Attitude among Italian Pediatric Dentists

Background: Pediatric dentists could play a key role in the prevention of human papilloma virus (HPV)-related oropharyngeal cancer (OP-cancer). The aim of this study was to assess knowledge, perception, and attitude on HPV-related OP-cancer, HPV infection, and HPV vaccination among Italian pediatric dentists. Methods: A cross-sectional study was conducted. Pediatric dentists received, by email, a link to participate in the questionnaire online. The questionnaire comprised four parts: (i) demographic information, (ii) knowledge on HPV-related OP-cancer, HPV infection, and HPV vaccine, (iii–iiii) perceptions and attitude on HPV-related OP-cancer, HPV infection, and HPV vaccine. Data were statistically analyzed with Kruskal–Wallis and Mann–Whitney test and Pearson’s chi-square test. Results: A total of 271 pediatric dentists completed the questionnaire. Results showed a good overall knowledge; a positive perception of their role in HPV disease prevention; a good attitude in discussing sensitive topics; a need for acquiring more information about HPV’s connection to cancer, HPV infection, and HPV vaccine. Conclusions: Improving educational training programs, as well as informing about prevention of HPV-related OP-cancer, will place pediatric dentists in the front line of HPV diseases primary prevention

Pharmacokinetics and pharmacodynamics of a 13-mer LNA-inhibitor-miR-221 in mice and non-human primates

Locked nucleic acid (LNA) oligonucleotides have been successfully used to efficiently inhibit endogenous small noncoding RNAs in vitro and in vivo. We previously demonstrated that the direct miR-221 inhibition by the novel 13-mer LNA-i-miR-221 induces significant antimyeloma activity and upregulates canonical miR-221 targets in vitro and in vivo. To evaluate the LNA-i-miR-221 pharmacokinetics and pharmacodynamics, novel assays for oligonucleotides quantification in NOD.SCID mice and Cynomolgus monkeys (Macaca fascicularis) plasma, urine and tissues were developed. To this aim, a liquid chromatography/mass spectrometry method, after solid-phase extraction, was used for the detection of LNA-i-miR-221 in plasma and urine, while a specific in situ hybridization assay for tissue uptake analysis was designed. Our analysis revealed short half-life, optimal tissue biovailability and minimal urine excretion of LNA-i-miR-221 in mice and monkeys. Up to 3 weeks, LNA-i-miR-221 was still detectable in mice vital organs and in xenografted tumors, together with p27 target upregulation. Importantly, no toxicity in the pilot monkey study was observed. Overall, our findings indicate the suitability of LNA-i-miR-221 for clinical use and we provide here pilot data for safety analysis and further development of LNA-miRNA-based therapeutics for human cancer

A familial form of epidermolysis bullosa simplex associated with a pathogenic variant in krt5

Epidermolysis bullosa simplex is a disease that belongs to a group of genodermatoses characterised by the formation of superficial bullous lesions caused by minor mechanical trauma to the skin. The skin fragility observed in the EBS is mainly caused by pathogenic variants in the KRT5 and KRT14 genes that compromise the mechanical stability of epithelial cells. By performing DNA sequencing in a female patient with EBS, we found the pathogenic variant c.967G>A (p.Val323Met) in the KRT5 gene. This variant co-segregated with EBS in the family pedigree and was transmitted in an autosomal dominant inheritance manner. This is the first report showing a familial form of EBS due to this pathogenic variant

Budd-Chiari syndrome in a 25-year-old woman with Behçet's disease: a case report and review of the literature

<p>Abstract</p> <p>Introduction</p> <p>The risk that patients with Behçet's disease will develop thrombotic complications has been previously described. Although it is distributed worldwide, Behçet's disease is rare in the Americas and Europe. Even though the pathogenic mechanisms of vascular complications of Budd-Chiari syndrome in patients with Behçet's disease are unknown, severe vascular complications of Budd-Chiari syndrome associated with Behçet's disease seem to affect mainly young men.</p> <p>Case presentation</p> <p>We report a case of Budd-Chiari syndrome, a severe vascular complication that developed in a 25-year-old Afro-Brazilian woman with Behçet's disease.</p> <p>Conclusion</p> <p>Severe vascular complications of Budd-Chiari syndrome in patients with Behçet's disease are much more common in young adult male patients; we present a rare case of Budd-Chiari syndrome in a young Afro-Brazilian woman with Behçet's disease.</p

Aurora Kinase A expression predicts platinum-resistance and adverse outcome in high-grade serous ovarian carcinoma patients

High-Grade Serous Ovarian Carcinoma (HGSOC) is the predominant histotype of epithelial ovarian cancer (EOC), characterized by advanced stage at diagnosis, frequent TP53 mutation, rapid progression, and high responsiveness to platinum-based-chemotherapy. To date, standard first-line-chemotherapy in advanced EOC includes platinum salts and paclitaxel with or without bevacizumab. The major prognostic factor is the response duration from the end of the platinum-based treatment (platinum-free interval) and about 10-0 % of EOC patients bear a platinum-refractory disease or develop early resistance (platinum-free interval shorter than 6 months). On these bases, a careful selection of patients who could benefit from chemotherapy is recommended to avoid unnecessary side effects and for a better disease outcome. In this retrospective study, an immunohistochemical evaluation of Aurora Kinase A (AURKA) was performed on 41 cases of HGSOC according to platinum-status. Taking into account the number and intensity of AURKA positive cells we built a predictive score able to discriminate with high accuracy platinum-sensitive patients from platinum-resistant patients (p &lt; 0.001). Furthermore, we observed that AURKA overexpression correlates to worse overall survival (p = 0.001; HR 0.14). We here suggest AURKA as new effective tool to predict the biological behavior of HGSOC. Particularly, our results indicate that AURKA has a role both as predictor of platinum-resistance and as prognostic factor, that deserves further investigation in prospective clinical trials. Indeed, in the era of personalized medicine, AURKA could assist the clinicians in selecting the best treatment and represent, at the same time, a promising new therapeutic target in EOC treatment

Elastofibroma dorsi: a histochemical and immunohistochemical study

Elastofibroma dorsi (ED) is considered a member of a heterogeneous group of benign fibrous (fibroblastic or myofibroblastic) soft-tissue tumors, frequently localized in the periscapular region in middle aged or older individuals. However, the pathogenesis of ED is still unclear and many authors believe that ED results from a reactive hyperproliferation of fibroblastic tissue, while others suggest that it may be a consequence of a mechanical friction. In our study, we examined 11 cases of ED using histochemical and immunohistochemical methods, in order to extend the knowledge about extracellular matrix composition and histopathogenesis of ED. From the results it appeared that stroma and interspersed spindle cells of ED were positive for both periostin and tenascin-C. Mast cells tryptase-positive were also abundant throughout the lesion. The perivascular distribution of periostin and tenascin-C, associated with the CD34 positivity, suggest that endothelial-mesenchymal transition events can account for neovascularization and production of fibroelastic tissue characteristic of elastofibroma. Our data obtained in endothelial cells cultures demonstrated that elastin production is higher when the status of confluence of the cells is low. So, we can assume that such a phenomenon is a characteristic of mesenchymal/endothelial cells CD34 positive, in which elastin production results to be inversely proportional to the vascular differentiation of cellular elements. In the light of these considerations, we think that a cancerous nature of ED is unlikely. Overall, our study report, for the first time, a detailed description of extracellular matrix composition in ED, suggesting that a mechanical strain-dependent reactivation of periostin and tenascin-C expression, as well as of elastin deposition, could be responsible for development of ED

EP-1430: Phase II study of short-course accelerated palliative radiation therapy for advanced thoracic tumors

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