Antonella Miriam Di Lullo

Genotype–phenotype correlation and functional studies in patients with cystic fibrosis bearing CFTR complex alleles

Background The effect of complex alleles in cystic fibrosis (CF) is poorly defined for the lack of functional studies. Objectives To describe the genotype–phenotype correlation and the results of either in vitro and ex vivo studies performed on nasal epithelial cells (NEC) in a cohort of patients with CF carrying cystic fibrosis transmembrane conductance regulator (CFTR) complex alleles. Methods We studied 70 homozygous, compound heterozygous or heterozygous for CFTR mutations: p.[Arg74Trp;Val201Met;Asp1270Asn], n=8; p.[Ile148Thr;Ile1023_Val1024del], n=5; p.[Arg117Leu;Leu997Phe], n=6; c.[1210-34TG[12];1210-12T[5];2930C>T], n=3; p.[Arg74Trp;Asp1270Asn], n=4; p.Asp1270Asn, n=2; p.Ile148Thr, n=6; p.Leu997Phe, n=36. In 39 patients, we analysed the CFTR gating activity on NEC in comparison with patients with CF (n=8) and carriers (n=4). Finally, we analysed in vitro the p.[Arg74Trp;Val201Met;Asp1270Asn] complex allele. Results The p.[Ile148Thr;Ile1023_Val1024del] caused severe CF in five compound heterozygous with a class I–II mutation. Their CFTR activity on NEC was comparable with patients with two class I–II mutations (mean 7.3% vs 6.9%). The p.[Arg74Trp;Asp1270Asn] and the p.Asp1270Asn have scarce functional effects, while p.[Arg74Trp;Val201Met;Asp1270Asn] caused mild CF in four of five subjects carrying a class I–II mutation in trans, or CFTR-related disorders (CFTR-RD) in three having in trans a class IV–V mutation. The p.[Arg74Trp;Val201Met;Asp1270Asn] causes significantly (p<0.001) higher CFTR activity compared with compound heterozygous for class I–II mutations. Furthermore, five of six compounds heterozygous with the p.[Arg117Leu;Leu997Phe] had mild CF, whereas the p.Leu997Phe, in trans with a class I–II CFTR mutation, caused CFTR-RD or a healthy status (CFTR activity: 21.3–36.9%). Finally, compounds heterozygous for the c.[1210-34TG[12];1210-12T[5];2930C>T] and a class I–II mutation had mild CF or CFTR-RD (gating activity: 18.5–19.0%). Conclusions The effect of complex alleles partially depends on the mutation in trans. Although larger studies are necessary, the CFTR activity on NEC is a rapid contributory tool to classify patients with CFTR dysfunction.

Diffusion-Weighted Intensity Magnetic Resonance in the Preoperative Diagnosis of Cholesteatoma

We have analyzed the preoperative diagnosis of cholesteatoma through the use of diffusion-weighted intensity magnetic resonance (DWI-MR) in 16 consecutive patients suffering from chronic otitis media with clinical and radiological (by computed tomography) suspicion of cholesteatoma. In particular, we compared the radiological data with intraoperative ones, verifying the correspondence (in terms of sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy) between what is reported by DWI-MR and what is actually detectable at the time of surgery. Furthermore, we identified the most reliable DWI-MR sequence [single-shot (SSh) echo planar imaging (EPI) vs. multi-shot turbo spin-echo not-EPI] to detect cholesteatoma and reduce the time for examination. The obtained data on computed tomography scans revealed low diagnostic accuracy (56%); DWI-MR, instead, showed higher values, especially using not-EPI sequences (93.75 vs. 68.75% obtained by SSh-EPI sequences).

Adenoid cystic carcinoma of the larynx in a 70-year-old patient: A case report

Adenoid cystic carcinoma (ACC) is a relatively rare tumor that accounts for <1% of all head and neck malignancies. Laryngeal localization of ACC, which is most commonly hypoglottic, is relatively rare, occurring in 0.07–0.25% of all laryngeal tumors. ACC is characterized as a slow-growing tumor with a high recurrence rate, which often causes dyspnea and hoarseness. ACC exhibits a propensity for perineural invasion and thus, patients may experience pain as a late symptom of the disease. Distant metastasis occurs in 35–50% of cases and the lungs are the most common site of metastasis. Tumors are usually diagnosed by physical examination with fiberoscopy and computed tomography of the neck and chest, due to the high rate of lung metastases. The standard therapy for ACC is surgery followed by radiotherapy. In this study, a 70-year-old patient presented with laryngeal ACC, who underwent total laryngectomy with bilateral neck dissection and adjuvant radiotherapy, is presented. Follow-up examination performed 2 years after surgery revealed no evidence of locoregional recurrence or distant metastases. Previously published literature regarding ACC of the larynx was also reviewed.

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.

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

BackgroundExtramedullary 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.Case presentationWe present three cases of sinonasal extramedullary plasmacytoma who underwent radiotherapy: a 61-year-old white man, a 60-year-old white man, and a 37-year-old white woman. We found long-term survival with stable disease in all three cases.ConclusionsThe management of solitary extramedullary plasmacytomas of the sinonasal tract is not well established yet. However, the possibility of recurrence and progression to multiple myeloma requires a thorough follow-up protocol. Due to the absence of a standardized protocol for these tumors, we tried to design a tailored long-term follow-up scheme.

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 receptors [3].

Cystic fibrosis, molecular genetics for all life

Cystic fibrosis (CF) is the most frequent lethal autosomal recessive disorder among Caucasians (incidence: 1:2,500 newborn). In the last two decades CF prognosis considerably improved and many patients well survive into their adulthood. Furthermore, milder CF with a late onset was described. CF is a challenge for laboratory of molecular genetics that greatly contributes to the natural history of the disease since fetal age. Carrier screening and prenatal diagnosis, also by non-invasive analysis of maternal blood fetal DNA, are now available, and many labs offer preimplantation diagnosis. The major criticism in prenatal medicine is the lack of an effective multidisciplinary counseling that helps the couples to plan their reasoned reproductive choice. Most countries offer newborn screening that significantly reduce CF morbidity but different protocols based on blood trypsin, molecular analysis and sweat chloride cause a variable efficiency of the screening programs. Again, laboratory is crucial for CF diagnosis in symptomatic patients: sweat chloride is the diagnostic golden standard, but different methodologies and the lack of quality control in most labs reduce its effectiveness. Molecular analysis contributes to confirm diagnosis in symptomatic subjects; furthermore, it helps to predict the disease outcome on the basis of the mutation (genotype-phenotype correlation) and mutations in a myriad of genes, inherited independently by CF transmembrane conductance regulator (CFTR), which may modulate the clinical expression of the disease in each single patient (modifier genes). More recently, the search of the CFTR mutations gained a role in selecting CF patients that may benefit from biological therapy based on correctors and potentiators that are effective in patients bearing specific mutations (personalized therapy). All such applications of molecular diagnostics confirm the “uniqueness” of each CF patient, offering to laboratory medicine the opportunity to reposition the patient in the “core” of the medical process. Proceedings of the 11 th International Workshop on Neonatology and Satellite Meetings · Cagliari (Italy) · October 26 th -31 st , 2015 · From the womb to the adult Guest Editors: Vassilios Fanos (Cagliari, Italy), Michele Mussap (Genoa, Italy), Antonio Del Vecchio (Bari, Italy), Bo Sun (Shanghai, China), Dorret I. Boomsma (Amsterdam, the Netherlands), Gavino Faa (Cagliari, Italy), Antonio Giordano (Philadelphia, USA)