Two CFTR mutations within codon 970 differently impact on the chloride channel functionality.

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.

Trans-heterozygosity for mutations enhances the risk of recurrent/chronic pancreatitis in patients with Cystic Fibrosis.

BACKGROUND: Recurrent (RP) and chronic pancreatitis (CP) may complicate Cystic Fibrosis (CF). It is still unknown if mutations in genes involved in the intrapancreatic activation of trypsin (IPAT) or in the pancreatic secretion pathway (PSP) may enhance the risk for RP/CP in patients with CF. METHODS: We enrolled: 48 patients affected by CF complicated by RP/CP and, as controls 35 patients with CF without pancreatitis and 80 unrelated healthy subjects. We tested a panel of 8 genes involved in the IPAT, i.e. PRSS1, PRSS2, SPINK1, CTRC, CASR, CFTR, CTSB and KRT8 and 23 additional genes implicated in the PSP. RESULTS: We found 14/48 patients (29.2%) with mutations in genes involved in IPAT in the group of CF patients with RP/CP, while mutations in such genes were found in 2/35 (5.7%) patients with CF without pancreatitis and in 3/80 (3.8%) healthy subjects (p < 0.001). Thus, we found mutations in 12 genes of the PSP in 11/48 (22.9%) patients with CF and RP/CP. Overall, 19/48 (39.6%) patients with CF and RP/CP showed one or more mutations in the genes involved in the IPAT and in the PSP while such figure was 4/35 (11.4%) for patients with CF without pancreatitis and 11/80 (13.7%) for healthy controls (p < 0.001). CONCLUSIONS: The trans-heterozygous association between CFTR mutations in genes involved in the pathways of pancreatic enzyme activation and the pancreatic secretion may be risk factors for the development of recurrent or chronic pancreatitis in patients with CF.

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.

Clinical expression of cystic fibrosis in a large cohort of Italian siblings.

BACKGROUND: A clinical heterogeneity was reported in patients with Cystic Fibrosis (CF) with the same CFTR genotype and between siblings with CF. METHODS: We investigated all clinical aspects in a cohort of 101 pairs of siblings with CF (including 6 triplets) followed since diagnosis. RESULTS: Severe 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. CONCLUSIONS: Physicians 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.

Cholesteatoma vs granulation tissue: a differential diagnosis by DWI-MRI apparent diffusion coefficient.

PURPOSE: To diagnose cholesteatoma when it is not visible through tympanic perforation, imaging techniques are necessary. Recently, the combination of computed tomography and magnetic resonance imaging has proven effective to diagnose middle ear cholesteatoma. In particular, diffusion weighted images have integrated the conventional imaging for the qualitative assessment of cholesteatoma. Accordingly, the aim of this study was to obtain a quantitative analysis of cholesteatoma calculating the apparent diffusion coefficient value. So, we investigated whether it could differentiate cholesteatoma from other inflammatory tissues both in a preoperative and in a postoperative study. METHODS: This study included 109 patients with clinical suspicion of primary or residual/recurrent cholesteatoma. All patients underwent preoperative computed tomography and magnetic resonance imaging with diffusion sequences before primary or second-look surgery to calculate the apparent diffusion coefficient value. RESULTS: We found that the apparent diffusion coefficient values of cholesteatoma were significantly lower than those of non cholesteatoma. In particular, the apparent diffusion coefficient median value of the cholesteatoma group (0.84 × 10- 3 mm2/s) differed from the inflammatory granulation tissue (2.21 × 10- 3 mm2/s) group (p < 2.2 × 10- 16). Furthermore, we modeled the probability of cholesteatoma by means of a logistic regression and we determined an optimal cut-off probability value of ~ 0.86 (specificity = 1.0, sensitivity = 0.97), corresponding to an apparent diffusion coefficient cut-off value of 1.37 × 10- 3 mm2/s. CONCLUSIONS: Our study has demonstrated that apparent diffusion coefficient values constitute a valuable quantitative parameter for preoperative differentiation of cholesteatomas from other middle ear inflammatory diseases and for postoperative diagnosis of recurrent/residual cholesteatomas.

Effect of liposomes, vitamins A and E nasal spray in reducing the healing time after septoplasty with concurrent turbinate surgery in adolescents.

BACKGROUND: This study evaluates endoscopic and quality of life (QoL) outcomes in two groups, composed by both allergic (A) and non-allergic (N-A) adolescents undergoing septoplasty with concurrent turbinate surgery by radiofrequency treated after surgery with nasal spray containing liposomes and vitamins A and E. METHODS: This double-blind randomized study was carried out on 40 patients (22 males, 18 females, mean age 15.5±1.0 years) undergoing septoplasty and volumetric tissue reduction of inferior turbinates by radiofrequency for post-traumatic deformities and severe nasal obstruction. We enrolled 20 subjects with positive skin prick tests and 20 with negative skin prick tests (SPT) to aeroallergens. All subjects underwent the Visual Analogue Scale (VAS) questionnaire and the nasal endoscopy score by Lund and Kennedy (LK) at baseline before surgery (T0) and 15 days (T15) and 21 days (T21) after treatment. After surgery, the nose was not packed and the day after surgery all subjects were randomized into two groups, experimental arm group I (GI) and control arm group II (GII) and given the treatment, nasal spray containing liposomes composed of phospholipids, fatty acids, and vitamin A and E for group I and saline solution (sodium chloride 0.9%) for group II. RESULTS: After therapy, the VAS and LK scores were better (P<0.05) in the investigational than in the control arm in both sub-groups (A and N-A). CONCLUSIONS: Our findings suggested that liposomal, vitamins A and E nasal spray improves the QoL in the early postoperative period, both in A and N-A sub-groups.

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).

Impact of the COVID-19 pandemic on paediatric otolaryngology: a nationwide study.

Objective: The COVID-19 pandemic profoundly modified the work routine in healthcare; however, its impact on the field of paediatric otorhinolaryngology (ORL) has been rarely investigated. The aim of this study was to assess the impact of COVID-19 on paediatric ORL. Methods: A questionnaire was developed by the Young Otolaryngologists of the Italian Society of ORL-Head and Neck Surgery (GOS). The questionnaire consisted of 26 questions related to workplace and personal paediatric ORL activities. The link was advertised on the official social media platforms and sent by e-mail to 469 Italian otolaryngologists. Results: The questionnaire was completed by 118 responders. During the pandemic, the main reduction was observed for surgical activity (78.8%), followed by outpatient service (16.9%). The conditions that were mostly impacted by a delayed diagnosis were respiratory infections in 45.8% of cases and sensorineural hearing loss in 37.3% of cases. Conclusions: Paediatric ORL was highly impacted by the COVID-19 pandemic, with a significant reduction of surgical and outpatient activities and a delay in time-sensitive diagnosis. Therefore, the implementation of new strategies, such as telemedicine, is recommended.

High-Definition 3D Exoscope in Pediatric Otorhinolaryngology: A Systematic Literature Review.

This PRISMA-compliant systematic review aimed to investigate the use of and the most common procedures performed with the novel 3D 4K exoscope in surgical pediatric head and neck settings. METHODS: Search criteria were applied to PubMed, EMBASE and the Cochrane Review databases and included all studies published up to January 2023 reporting 3D 4K exoscope-assisted surgeries in pediatric patients. After the removal of duplicates, selection of abstracts and full-text articles, and quality assessment, we reviewed eligible articles for number of patients treated, age, surgical procedures, and outcomes. RESULTS: Among 54 potentially relevant records, 5 studies were considered eligible and included in this systematic review, with reported treatment data for 182 patients. The surgical procedures belong to the otologic field (121 cases), head and neck surgery (25 cases) and transoral surgery (36 cases). Exoscopy allowed high quality visualization of anatomical structures during cochlear implantation and during reconstruction in head and neck surgery; moreover, it improved the surgical view of surgeons, spectators and ENT students. CONCLUSIONS: The use of 3D 4K exoscopy has shown promising potential as a valuable tool in pediatric ORL-head and neck surgery; nevertheless, further validation of these encouraging outcomes is necessary through larger-scale studies specifically focused on pediatric patients.

Quality of Life Assessment of Chronic Otitis Media Patients Following Surgery.

Chronic otitis media (COM) is a persistent inflammation of the middle ear. COM often requires surgical management and represents one of the most disabling pathologies in the field of otolaryngology, not only due to hearing loss but also because recurrent otorrhea seriously affects the quality of life (QoL) of patients. The COMOT-15 questionnaire is a reliable, valid and sensitive tool for measuring the QoL of patients with COM. The aim of this study was to evaluate QoL by using the Italian version of the COMOT-15 in COM patients undergoing surgery based on age and different operation techniques. This observational retrospective study involved fifty-two consecutive patients undergoing surgical treatment for COM according to Nadol criteria. Preoperatively (T0) and 12 months after surgery (T1) patients underwent clinical examination, imaging, the Italian version of the COMOT-15 and pure tone audiometry. After surgery, we observed an improvement of QoL in 84.6% of the population. The COMOT-15 overall score, ear symptoms and hearing subscores showed significantly better ratings after surgery in the whole analyzed group. However, the separate analysis of patients operated with open techniques and closed techniques showed a significant improvement in ear symptoms subscore in both groups and a significant improvement in hearing subscore and mental health subscore only in patients operated on with closed techniques. Moreover, we observed a positive correlation between age and Δ-COMOT. This study shows the crucial role of a reliable and suitable questionnaire such as the COMOT-15 in evaluating COM patients, including clinical symptoms, functional and psychological impairments and highlighting a positive correlation between age and COMOT-15 results.

Postoperative infectious complications in head and neck cancer surgery.

AIM: In our work we have considered the problems related to the post-operative hospitalization in patients admitted to our ENT's department in the last 4 years. MATERIAL OF STUDY: Our observations refer to a sample of 155 patients suffering from head and neck tumors. RESULTS: Regarding therapy, some drugs have been less effective to prevent post-operative infection: the ceftriaxone at the level of the oral cavity/oropharynx and ceftriaxone/pefloxacin at the level of the hypopharynx/larynx. DISCUSSION: Post-operative infections in cancer surgery can compromise not only the surgical outcome but also be responsible for delays for any adjuvant treatments. Post-operative infections risk in head-neck cancer surgery drops from 30- 80 % to 20 % with perioperative antibiotic prophylaxis. Despite the introduction of pre-operative prophylaxis , according to guidelines, the number of post-surgical infections still remains high (40/61% of cases). It is important to know the intrinsic risk factors (related to the patient) and extrinsic (related to the external environment and the same procedure) to better understand how to prevent infections. Prolonged hospitalization can expose patients to the risk of hospital pathogens. CONCLUSION: We tried to outline a profile of head-neck cancer patients more likely to contract post-operative infections. We also compared the effects of various antibiotics administered before and after the onset of complications to suggest a therapeutic protocol. KEY WORDS: Antibiotics therapy Post-operative infectious, Prophylaxis in head and neck surgery.

Elexacaftor-Tezacaftor-Ivacaftor Therapy for Cystic Fibrosis Patients with The F508del/Unknown Genotype.

The new CFTR modulator combination, elexacaftor/tezacaftor/ivacaftor (Trikafta) was approved by the FDA in October 2019 for treatment of Cystic Fibrosis in patients 6 years of age or older who have at least one F508del mutation in one allele and a minimal-function or another F508del mutation in the other allele. However, there is a group of patients, in addition to those with rare mutations, in which despite the presence of a F508del in one allele, it was not possible to identify any mutation in the other allele. To date, these patients are excluded from treatment with Trikafta in Italy, where the CF patients carrying F508del/unknown represent about 1.3% (71 patients) of the overall Italian CF patients. In this paper we show that the Trikafta treatment of nasal epithelial cells, derived from F508del/Unknown patients, results in a significant rescue of CFTR activity. Based on our findings, we think that the F508del/Unknown patients considered in this study could obtain clinical benefits from Trikafta treatment, and we strongly suggest their eligibility for this type of treatment. This study, adding further evidence in the literature, once again confirms the validity of functional studies on nasal cells in the cystic fibrosis theratyping and personalized medicine.

Computed-Tomography-Structured Reporting in Middle Ear Opacification: Surgical Results and Clinical Considerations From a Large Retrospective Analysis.

Purpose: The aim of the study is to compare the accuracy of unstructured preoperative Computed Tomography (CT) reports from non-tertiary diagnostic centers with intraoperative findings in a large cohort of patients with Chronic Otitis Media (COM) undergone surgery. Methods: From 2012 to 2019, a total number of 301 patients were considered for our purposes. All patients with clinical evidence of COM had preoperative non-contrast high resolution CT scan of the temporal bone in non-tertiary diagnostic centers, performed within 3 months before surgery. Results: The accuracy of CT reports was analyzed in terms of nature, anatomical site, disease extension, bony erosion, vascular structures abnormalities relevant to surgical planning, and Eustachian tube patency. Compared to post-surgical findings, CT reporting critical analysis revealed a tendency to overestimation of bony erosion, coupled to underestimated description of facial canal/lateral semi-circular canal, vascular structures, and Eustachian tube. Conclusion: Discrepancies between CT reports and surgical findings in middle ear opacification can be at least in part due to limited expertise of general radiologists in ENT neuroimaging. To limit this lack of information and the limited accuracy of middle ear structures depiction, here we propose a structured checklist to adopt in the case of a temporal bone CT scan for COM, in order to optimize the communication with surgeons and provide all the crucial information for an accurate surgical planning.

Skull Base Fungal Osteomyelitis: A Case Report and Review of the Literature.

Skull base osteomyelitis (SBO) is an invasive infection refractory to therapy, closely linked with malignant otitis externa (MOE). It is characterized by a mild clinical presentation that can delay cross-sectional imaging considered as the key to revealing it. Skull base osteomyelitis typically affects elderly diabetics and immunocompromised patients (>70 years). It most commonly has an otogenic origin due to an extension of MOE. The prognosis can be very poor without the administration of adequate and timely therapy at an early disease stage. Nowadays, Pseudomonas aeruginosa remains the most common pathogen associated with SBO. Fungi are a rare cause of MOE. This report documents a rare case of otogenic SBO caused by Candida parapsilosis in a diabetic patient, with persistent otologic symptoms as clinical onset and resistance to medical treatment. Fungal MOE has more subtle symptoms and is more aggressive than its bacterial counterpart. When MOE is resistant to antibacterial drugs, this should raise the suspicion of a fungal etiology of MOE. The current guidelines do not exhaustively describe the diagnosis, antifungal drugs of choice, and optimum duration of treatment. The description of these rare clinical cases should help with the multidisciplinary management of this disease in order to optimize the diagnosis and therapeutic protocol.

Assisting PNA transport through cystic fibrosis human airway epithelia with biodegradable hybrid lipid-polymer nanoparticles.

Cystic fibrosis (CF) is characterized by an airway obstruction caused by a thick mucus due to a malfunctioning Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein. The sticky mucus restricts drugs in reaching target cells limiting the efficiency of treatments. The development of new approaches to enhance drug delivery to the lungs represents CF treatment's main challenge. In this work, we report the production and characterization of hybrid core-shell nanoparticles (hNPs) comprising a PLGA core and a dipalmitoylphosphatidylcholine (DPPC) shell engineered for inhalation. We loaded hNPs with a 7-mer peptide nucleic acid (PNA) previously considered for its ability to modulate the post-transcriptional regulation of the CFTR gene. We also investigated the in vitro release kinetics of hNPs and their efficacy in PNA delivery across the human epithelial airway barrier using an ex vivo model based on human primary nasal epithelial cells (HNEC) from CF patients. Confocal analyses and hNPs transport assay demonstrated the ability of hNPs to overcome the mucus barrier and release their PNA cargo within the cytoplasm, where it can exert its biological function.

The CO2-laser in the treatment of laryngeal and tracheal stenosis Our personal experiences.

AIM: In the last twenty years, the statement of the CO2 laser in laryngeal microsurgery has proved particularly useful in the surgical treatment of laryngotracheal stenosis. The Authors report their surgical experiences and discuss them considering the location, size and pathologic features of the disease. The aim of this study was to evaluate the results that may be obtained in the treatment of laryngotracheal stenosis by endoscopy using the CO2 laser, and analyze the advantages and limitations of surgical methods implemented. MATERIAL OF STUDY: It includes 128 patients treated from 1981 to 2016 by endoscopy using the CO2 laser. RESULTS: The healing occurred in 121 of the 128 patients (94.5%); in the remaining 7 cases (5.5%) - 4 subjects (3.1%) with supraglottic cicatricial stenosis and 3 patients (2.3%) with widespread laryngotracheal stenosis - it had to integrate the technique of endoscopic surgery with a traditional surgery of recovery. In particular, it has observed as follows: In supraglottic stenosis: - oedematous forms healed without difficulty, a limited number of controls (1-2) was necessary to practice and any type of stent has not been used; - cicatricial forms required a greater number of controls (3-6) and the execution in 2 cases (1.6%) of an arytenoidectomy, we had 4 failures (3.1%) for which it had to implement a recovery surgery of traditional type; In glottic/ipoglottic stenosis: - all oedematous forms healed with a number of checks less than 3, without use of stents; - scarring forms resolved after a higher number of controls (3-6), in 4 of them (3.1%) it was necessary to practice an arytenoidectomy (associated to exeresis of 1/3 posterior ipsilateral true vocal cord) and in 4 (3.1%) had to applied an endolaryngeal guardian (in one case a Traissac stent and in 3 ones a Montgomery T-tube); In tracheal stenosis has occurred healing in all cases, more specifically: - in limited forms to the third anterior of the trachea were enough 1-2 checks and it was not necessary using stent; - in extended forms (involvement of the 2/3 anterior and/or of the whole tracheal circumference) a higher number of controls (3-6) was necessary; - in concentric forms, with total obstruction of the lumen, the application of endoluminal stent (3 Montgomery T-tubes and 2 tracheal cannulas of Silastic) was always necessary in addition to a number of controls superior to 7. - In laryngotracheal spread forms, 3 failures (2.3%) recorded, in all cases, however, many controls (greater than 7) was necessary and a Montgomery T-tube was placed. CONCLUSIONS: The introduction of the CO2 laser in the surgical treatment of laryngotracheal stenosis has undoubtedly improved the chances of endoscopic surgery; it is currently able to offer significant advantages compared to traditional techniques (cures faster, less traumatic interventions, post-operative elapsed better tolerated by patients, etc.) but it is also indisputable that to ensure the success of these operations is essential a correct understanding of the size and pathologic features of the same stenosis: the data, in fact, affect the choice of surgical addresses to adopt in individual cases and the prognostic judgment. KEY WORDS: Airway management, Airway problems, CO2 laser, Direct laryngoscopy, Endoscopy, External surgical approach, Laryngotracheal stenosis, Minimally invasive surgery, Montgomery Safe T-tube, Tracheal stenosis, Tracheostomy.

Clinical management of extrapleural septal solitary fibrous tumor: A case report.

Solitary fibrous tumor (SFT) is a rare neoplasm arising from the pleura, although it can sometimes affect extrapleural sites, including the head and neck. The sinonasal involvement is exceptional. Recent literature defines the SFT as a single spectrum of mesenchymal tumors, including hemangiopericytoma, which is currently considered a cellular phenotypic variant. The current case describes a rare case of a nasal septal SFT. The mass was embolized and then removed through endonasal endoscopic surgery. Histopathologic examination demonstrated positive immunoreactivity for CD34, and negative for keratin and S100 protein confirming the diagnosis of benign nasal SFT. After two years of follow-up, no relapse was observed. Diagnostic assessment of SFT requires nasal endoscopy, imaging and histopathological examination and a long time follow up is mandatory.

Unusual Localization of an Emergent Bacterium, Raoultella ornithinolytica.

Raoultella ornithinolytica is a bacterium belonging to the family Enterobacteriacae. It is a rare but emergent cause of human pathologies especially in immunocompromised patients. We described the first case in the literature of isolated external otitis sustained by Raoultella ornithinolytica in an immunocompetent host. A 54-year-old Caucasian man with a history of previous myringoplasty came to our attention reporting otalgia and otorrhea. We performed right ear swab for culture examination, meanwhile we started empirical therapy with topic administration of neomycin, without any clinical improvement. The cultural examination showed the presence of a Raoultella ornithinolytica infection. After ten days of treatment with oral ciprofloxacin and topic levofloxacin, there was the complete resolution of pain and inflammation. Raoultella ornithinolytica must be taken into consideration as an emergent cause of human infection, also in case of external otitis. Infection can be severe and can occur both in immunocompromised and in immunocompetent hosts. Culture test is mandatory to choose the proper therapy and avoid potential severe complications.

Apparent diffusion coefficients for predicting primary cholesteatoma risk of recurrence after surgical clearance.

PURPOSE: Beside the well-known accuracy of non-EPI DWI techniques and relative ADC maps in detecting cholesteatomatous tissue, ADC can also represent a useful tool for stratifying cholesteatoma risk of recurrence. Aim of this study is to test the role of ADC in determining risk of recurrence for primary middle ear cholesteatoma, proposing stratification based on pre-operative mean (mADC) and normalized (nADC) ADC values. METHODS: In this prospective study, 60 patients with primary unilateral middle ear cholesteatoma underwent a three-years-long follow-up to assess the presence of recurrent disease after macroscopically complete excisional surgery. Baseline MRI examination mADC and nADC values in the group with early evidence of recurrent cholesteatoma were compared to the group with no evidence of recurrence by using T statistics. RESULTS: ADC values on pre-operative MRI examination were lower in cholesteatomas with early evidence of recurrence, and statistical significance was slightly higher for nADC compared to mADC measurements. We also determined a cut-off between the two groups, proposing stratification in high-risk of recurrence cholesteatomas (mADC≤ 1000 or nADC< 1.3) and low-risk cholesteatomas (mADC>1000 or nADC≥1.3). CONCLUSIONS: ADC values resulted discriminating in identifying cholesteatomas with higher risk of early recurrence, both for mean and normalized ADC, with optimized tissue characterization and outcome prediction.