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Pharmacological rescue of mutant cystic fibrosis transmembrane conductance regulator (CFTR) in cystic fibrosis (CF) depends on the specific defect caused by different mutation classes. We asked whether a patient with the rare p.Gly970Asp (c.2909G>A) mutation could benefit from CFTR pharmacotherapy since a similar missense mutant p.Gly970Arg (c.2908G>C) was previously found to be sensitive to potentiators in vitro but not in vivo. By complementary DNA transfection, we found that both mutations are associated with defective CFTR function amenable to pharmacological treatment. However, analysis of messenger RNA (mRNA) from patient's cells revealed that c.2908G>C impairs RNA splicing whereas c.2909G>A does not perturb splicing and leads to the expected p.Gly970Asp mutation. In agreement with these results, nasal epithelial cells from the p.Gly970Asp patient showed significant improvement of CFTR function upon pharmacological treatment. Our results underline the importance of controlling the effect of CF mutation at the mRNA level to determine if the pharmacotherapy of CFTR basic defect is appropriate.

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.

BackgroundA clinical heterogeneity was reported in patients with Cystic Fibrosis (CF) with the same CFTR genotype and between siblings with CF.MethodsWe investigated all clinical aspects in a cohort of 101 pairs of siblings with CF (including 6 triplets) followed since diagnosis.ResultsSevere lung disease had a 22.2% concordance in sib-pairs, occurred early and the FEV1% at 12 years was predictive of the severity of lung disease in the adulthood. Similarly, CF liver disease occurred early (median: 15 years) and showed a concordance of 27.8% in sib-pairs suggesting a scarce contribution of genetic factors; in fact, only 2/15 patients with liver disease in discordant sib-pairs had a deficiency of alpha-1-antitrypsin (a known modifier gene of CF liver phenotype). CF related diabetes was found in 22 pairs (in 6 in both the siblings). It occurred later (median: 32.5 years) and is strongly associated with liver disease. Colonization by P. aeruginosa and nasal polyposis that required surgery had a concordance > 50% in sib-pairs and were poorly correlated to other clinical parameters. The pancreatic status was highly concordant in pairs of siblings (i.e., 95.1%) but a different pancreatic status was observed in patients with the same CFTR mutations. This suggests a close relationship of the pancreatic status with the “whole” CFTR genotype, including mutations in regulatory regions that may modulate the levels of CFTR expression. Finally, a severe course of CF was evident in a number of patients with pancreatic sufficiency.ConclusionsPhysicians involved in care of patients with CF and in genetic counseling must be aware of the clinical heterogeneity of CF even in sib-pairs that, at the state of the art, is difficult to explain.Electronic supplementary materialThe online version of this article (10.1186/s12890-018-0766-6) contains supplementary material, which is available to authorized users.

Lipoma is a common benign tumor affecting the soft tissues arising in every location where fat is normally present. About 15% of lipomas occur in head and neck region. The lipoma of parotid gland is a rare entity, comprising 0.6%-4.4% of all parotid tumors. The etiology remains unclear. The case described a lipoma of the superficial lobe of the parotid gland in a 46-year-old male.

Background Cystic fibrosis (CF) is a multisystem disease that involves the upper airways with chronic rhinosinusitis (CRS) causing nasal congestion, rhinorrhea, mouth breathing, facial pain, and olfactory dysfunction. Twelve percent to 71% of CF patients report smelling alterations with an impact on nutrition and quality of life. Objectives The goal was to study olfaction performance in CF patients with CRS that worsens quality of life. Methods A total of 121 subjects were enrolled in this study. Seventy-one had CF and underwent ear, nose, and throat evaluation with nasal endoscopy, sinonasal outcome test 22 (SNOT-22), visual analog scale (VAS), and “Sniffin’ Sticks.” Fifty subjects were age-matched with healthy controls. Results All 71 CF patients were affected by CRS; 59 of 71 (83.1%) had CRS without nasal polyps and 12 of 71 (16.9%) had CRS with early nasal polyps. None of the 50 controls had CRS. Total SNOTT-22 mean values in the 71 CF patients were 38.10 ± 21.08 points. If considering only the 59 CF patients without nasal polyps, the SNOTT-22 mean value was 36.76 ± 21.52 points. Moreover, based on the VAS scores, the degree of nasal symptoms was classified as mild for facial pain, smell alteration, nasal discharge, and sneezing and resulted in moderate symptoms for nasal blockage and headache. Among the CF patients, 55 of 71 (76.5%) declared to be normosmic, while the smelling ability assessed by “Sniffin’ Sticks” showed that only 4 of 71 (5.63%) were normosmic, 58 (81.69%) were hyposmic, and 9 (12.68%) were anosmic. In the controls, 41(82%) were normosmic, 9 (18%) were hyposmic, and none were reported to be anosmic ( P < .001). Conclusions We confirm that most CF patients have a relevant olfactory impairment, although only a low percentage declares such alteration. A careful evaluation with simple and rapid tests helps to select the patients who may benefit from specific therapies.

The clinical manifestation of cystic fibrosis (CF) is heterogeneous also in patients with the same cystic fibrosis transmembrane regulator (CFTR) genotype and in affected 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 significantly 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 modifier gene of sinonasal disease severity and of pulmonary P. aeruginosa colonization in patients with CF.

Introduction and Purpose. Diffusion weighted imaging (DWI) has been proven to be valuable in the diagnosis of middle ear cholesteatoma. The aims of our study were to evaluate the advantage of multi-shot turbo spin echo (MSh TSE) DWI compared to single-shot echo-planar (SSh EPI) DWI for the diagnosis of cholesteatoma. Material and Methods. Thirty-two patients with clinical suspicion of unilateral cholesteatoma underwent preoperative MRI (1.5T) with SSh EPI and MSh TSE. Images were separately analyzed by 4 readers with different expertise to confirm the presence of cholesteatoma. Sensitivity, specificity, diagnostic accuracy, and positive (PPV) and negative predictive values (NPV) were assessed for each observer and interrater agreement was assessed using kappa statistics. Diagnosis was obtained at surgery. Results. Overall MSh TSE showed higher diagnostic accuracy and lower negative predictive value (NPV) compared to conventional SSh EPI. Interreader agreement between the observers revealed the superiority of MSh TSE compared to SSh EPI. Interrater agreement among all the four observers was higher by using MSh TSE compared to SSh EPI. Conclusion. Our findings suggest that MSh TSE DWI has higher sensitivity for detection of cholesteatoma and lower probability of misdiagnosis. MSh TSE DWI is useful in guiding less experienced observers to the diagnosis.