Nasal epithelial cells: an “ex vivo model” contributing to the diagnosis and evaluation of new drugs in Cystic Fibrosis

Cystic Fibrosis (CF) is an autosomal recessive disease caused by mutations in the cystic fibrosis transmembrane regulator (CFTR) gene. About 2000 mutations have been described so far. We set up the ex vivo model of human nasal epithelial cells (HNECs) to test the effect of novel mutations and to evaluate the effect of molecular therapies in cells from patients with CF bearing specific genotypes. We improved the sampling (by brushing), culture and analysis of HNECs using several techniques to study the effect of CFTR mutations. We performed 223 brushings from patients with CF and controls. Using cultured cells we: i) demonstrated the widely heterogeneous expression of CFTR in patients and in controls; ii) defined the splicing effect of a CFTR mutation; iii) assessed the CFTR gating activity of HNECs from patients bearing different mutations; iv) demonstrated that butyrate significantly enhances CFTR expression; v) described the genotype-phenotype correlation and the results of either in vitro and ex vivo studies performed on HNECs in a large group of patients with CF carrying CFTR complex alleles. According to our data we can conclude: 1) the HNEC brushing is performed without anesthesia and it is well tolerated by children and adults; 2) once sampled, HNECs may be stored up to 48 hours before culture. This allows multicenter studies; 3) the HNECs culture is a suitable model to study the molecular effect of novel CFTR mutations and/or mutations of uncertain significance; 4) the ex-vivo model of HNECs may be used to evaluate, before the use in humans, the effect of novel drugs on cells bearing specific CFTR mutations; 5) our procedure may be used for the quantitative measurement of the CFTR gating activity of the HNECs from patients with different genotypes. It may help to classify: i) CF patients bearing two severe mutations, with an activity <10%; ii) CF patients bearing at least a mild mutation, with an activity of 10-30%; iii) CF carriers (heterozygous subjects) with an activity between 40-70%

Epidermal cyst of temporal bone as a delayed complication of myringoplasty

Epidermal cysts are benign tumors derived from the epidermis or the epithelial hair follicle filled with keratin and lipid-rich debris, typically occurring in areas with a high-density of sebaceous glands. These cysts commonly occur on the face, scalp, neck and trunk, where the sebaceous glands are more active. Their localization within the bone is extremely uncommon. The current study details the case of a 24-year-old male who presented with right otorrhea and ipsilateral hypoacusia having undergone right overlay myringoplasty for subtotal eardrum perforation. This patient represents a rare case of an epidermal cyst localized in the temporal bone (the fifth described in English-language literature), which may be considered as a complication of myringoplasty

Immunohistochemical patterns in the differential diagnosis of rhinopharyngeal granulocytic sarcoma

Granulocytic sarcoma (GS) is a rare extramedullary manifestation of acute myeloid leukemia (AML). GS may develop simultaneously to AML or as a relapse of leukemia, particularly following allogeneic hematopoietic stem cell transplant. Subperiosteal bone, lymph nodes and skin are commonly involved, whereas rhinopharyngeal involvement is less common, with only 14 cases reported in the literature. Due to its rarity, rhinopharyngeal GS may lead to diagnostic pitfalls, particularly when it is poorly differentiated or is without concomitant marrow involvement. Thus, immunohistochemical findings play a key role in diagnosis. The current report describes a case of a 53-year-old female suffering from rhinopharyngeal GS and with a history of AML treated with chemotherapy and radiotherapy, focusing on the importance of the immunohistochemical pattern to assess the right diagnosis. Recent studies have demonstrated that the immunophenotype is of utmost importance for the diagnosis of GS. The high expression of myeloperoxidase (MPO) is common in GS; however, ~30% of GSs do not contain MPO. Therefore, the presence of other markers is required to confirm the diagnosis of GS

MANAGEMENT DELLO SCHWANNOMA INTRALABIRINTICO

Lo schwannoma intralabirintico (SIL) è un raro tumore benigno (prevalenza 0.1-0.4%) che origina dalle cellule di Schwann perineurali del nervo cocleovestibolare prossimale al labirinto membranoso (coclea, vestibolo o canali semicircolari). E’ stato descritto per la prima volta da Meter nel 1917. I sintomi clinici di esordio includono ipoacusia neurosensoriale monolaterale progressiva (95%) e in alcuni casi improvvisa o fluttuante, acufeni (51%), disequilibrio (35%), vertigine (22%), fullness (2%). Alla risonanza magnetica (RM) il tumore si presenta come una massa circoscritta, ipointensa nelle sequenze T2-pesate e con un forte enhancement dopo somministrazione di gadolinio nelle immagini T1-pesate. Lo SIL si pone in diagnosi differenziale con M. di Meniere o neurite vestibolare. La mancanza di sintomi specifici e il lento pattern di crescita spiega la diagnosi tardiva. Oggigiorno la RM permette una diagnosi sempre più precoce e l’ adozione di un appropriato protocollo terapeutico

Intralabyrinthine Schwannoma of the Intravestibular Subtype: A Difficult Diagnosis

Intralabyrinthine schwannoma is a rare, slow-growing, benign tumor that affects the most terminal portions of the vestibular and cochlear nerves. It can be located in the vestibule, cochlea, or semicircular canals. In 2004, Kennedy et al proposed a classification system which recognized 7 subtypes of intralabyrinthine schwannoma; in 2013, Abel et al1 modified the Kennedy classification,2 which included intracochlear, intravestibular (IV), intravestibulocochlear, transmodiolar, transmacular, transotic, and tympanolabyrinthine, to also include translabyrinthine, tumors extending into the CPA, and tumors not otherwise specified. They also proposed to rename intralabyrinthine schwannoma as primary inner ear schwannoma to permit clear subsite categorization. Patients usually have nonspecific symptoms, including hearing loss, tinnitus, and only single episode of vertigo. Among the resulting symptoms, the most frequent is hearing loss, which affects 95% of the patients. Most times, this loss is slow and progressive, but it may be sudden or fluctuating. Less common symptoms include tinnitus (51%), imbalance (35%), vertigo (22%), and ear fullness (2%), which may be present alone or in combination.3-7 We report a rare case of a patient with hearing loss and single episode of vertigo secondary to the intralabyrinthine schwannoma of the IV subtype

Molecular Analysis of Prothrombotic Gene Variants in Venous Thrombosis: A Potential Role for Sex and Thrombotic Localization

Background: Requests to test for thrombophilia in the clinical context are often not evidence-based. Aim: To define the role of a series of prothrombotic gene variants in a large population of patients with different venous thromboembolic diseases. Methods: We studied Factor V Leiden (FVL), FVR2, FII G20210A, Methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C, beta-fibrinogen -455 G>A, FXIII V34L, and HPA-1 L33P variants and PAI-1 4G/5G alleles in 343 male and female patients with deep vein thrombosis (DVT), 164 with pulmonary embolism (PE), 126 with superficial vein thrombosis (SVT), 118 with portal vein thrombosis (PVT), 75 with cerebral vein thrombosis (CVT) and 119 with retinal vein thrombosis (RVT), and compared them with the corresponding variants and alleles in 430 subjects from the general population. Results: About 40% of patients with DVT, PE and SVT had at least one prothrombotic gene variant, such as FVL, FVR2 and FII G20210A, and a statistically significant association with the event was found in males with a history of PE. In patients with a history of PVT or CVT, the FII G20210A variant was more frequent, particularly in females. In contrast, a poor association was found between RVT and prothrombotic risk factors, confirming that local vascular factors have a key role in this thrombotic event. Conclusions: Only FVL, FVR2 and FII G20210A are related to vein thrombotic disease. Other gene variants, often requested for testing in the clinical context, do not differ significantly between cases and controls. Evidence of a sex difference for some variants, once confirmed in larger populations, may help to promote sex-specific prevention of such diseases

CO2 Modulates the Central Neural Processing of Sucrose Perception

The five universally accepted tastes, sweet, salty, sour, bitter, and umami (a savory sensation elicited by monosodium glutamate) have specific receptors in oral, pharyngeal and laryngeal regions [1]. The most credited candidates to the function of human primary taste cortex are the frontal operculum and the anterior insula; while the opercular cortex and the orbitofrontal cortex are thought to code for secondary gustatory functions, while the amygdale and the dorsolateral prefrontal cortex are involved as hierarchically superior processing units [2]. Conversely, more is known on the peripheral pathway of taste, including the molecular dynamics of many receptor

TAS2R38 is a novel modifer gene in patients with cystic fbrosis

The clinical manifestation of cystic fbrosis (CF) is heterogeneous also in patients with the same cystic fbrosis transmembrane regulator (CFTR) genotype and in afected sibling pairs. Other genes, inherited independently of CFTR, may modulate the clinical manifestation and complications of patients with CF, including the severity of chronic sinonasal disease and the occurrence of chronic Pseudomonas aeruginosa colonization. The T2R38 gene encodes a taste receptor and recently its functionality was related to the occurrence of sinonasal diseases and upper respiratory infections. We assessed the T2R38 genotype in 210 patients with CF and in 95 controls, relating the genotype to the severity of sinonasal disease and to the occurrence of P. aeruginosa pulmonary colonization. The frequency of the PAV allele i.e., the allele associated with the high functionality of the T2R38 protein, was signifcantly lower in i) CF patients with nasal polyposis requiring surgery, especially in patients who developed the complication before 14 years of age; and ii) in CF patients with chronic pulmonary colonization by P. aeruginosa, especially in patients who were colonized before 14 years of age, than in control subjects. These data suggest a role for T2R38 as a novel modifer gene of sinonasal disease severity and of pulmonary P. aeruginosa colonization in patients with CF

Osteoma del mascellare associato a cisti odontogena omolaterale: approccio chirurgico combinato.

L’osteoma osteoide è una lesione osteogenica benigna la cui localizzazione nel seno mascellare è piuttosto rara, appena 7 casi descritti negli ultimi 15 anni. Di più frequente riscontro, sono le cisti odontogene del mascellare. Il riscontro contestuale delle due patologie è un evento piuttosto raro. Descriviamo il caso di osteoma del mascellare associato a voluminosa cisti odontogena omolaterale a partenza dalla radice dell’11mo. La paziente (42a), giungeva alla nostra osservazione per ostruzione respiratoria nasale, cacosmia, rinorrea mucopurulenta ed epifora monolaterali. L’imaging evidenziava la presenza di entrambe le lesioni che occupavano interamente il seno mascellare destro. La paziente veniva indirizzata a chirurgia e si optava per un approccio endoscopico combinato con doppio accesso transorale e transnasale con exeresi delle lesioni e ricostruzione del pavimento del mascellare con ausilio di membrana con PRGF (plasma ricco di fattori di crescita). Nessuna complicanza peri e post-operatoria è stata osservata. Il caso in esame pone l’attenzione sull’approccio multidisciplinare alla patologia e sulla scelta di una tecnica chirurgica conservativa con utilizzo di PRGF

Strategy for the treatment and follow-up of sinonasal solitary extramedullary plasmacytoma: a case series

Extramedullary plasmacytoma is a rare neoplasm characterized by monoclonal proliferation of plasma cells outside bone marrow. It accounts for 4% of all non-epithelial sinonasal tumors. According to the literature, radiotherapy is the standard therapy for extramedullary plasmacytoma. However, the conversion rate of extramedullary plasmacytoma to multiple myeloma is reported to be between 11 and 33% over 10 years. The highest risk of conversion is reported during the first 2 years after diagnosis, but conversion has been noted up to 15 years after diagnosis. Once conversion to multiple myeloma is complete, less than 10% of patients will survive 10 years