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Hintergrund: Die Photodynamische Therapie (PDT) ist eine onkologische Behandlungsmethode die auf der Aktivierung eines photosensibilisierenden Stoffes durch einen Lichtstrahl basiert. Die Reaktion produziert einen Schaden im Gewebe das den Stoff beinhaltet. Der erster angewendete photosensibilisierender[for full text, please go to the a.m. URL], 96. Jahrestagung der Vereinigung Südwestdeutscher Hals-Nasen-Ohrenärzte

Die photodynamische Therapie (PDT) ist eine neue Behandlungsmöglichkeit für Tumoren im Kopf- und Halsbereich. Sie basiert sich auf die Lichtaktivierung einer photosensiblen Substanz, die die Tumorzellen zur Nekrotisierung bringt. Die PDT ist in Italien nur als palliative Behandlung zugelassen[for full text, please go to the a.m. URL], 83. Jahresversammlung der Deutschen Gesellschaft für Hals-Nasen-Ohren-Heilkunde, Kopf- und Hals-Chirurgie

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. 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.

Objective To perform an extensive search for genomic rearrangements by microarray-based comparative genomic hybridization in patients with epilepsy. Design Prospective cohort study. Setting Epilepsy centers in Italy. Patients Two hundred seventy-nine patients with unexplained epilepsy, 265 individuals with nonsyndromic mental retardation but no epilepsy, and 246 healthy control subjects were screened by microarray-based comparative genomic hybridization. Main Outcomes Measures Identification of copy number variations (CNVs) and gene enrichment. Results Rare CNVs occurred in 26 patients (9.3%) and 16 healthy control subjects (6.5%) (P = .26). The CNVs identified in patients were larger (P = .03) and showed higher gene content (P = .02) than those in control subjects. The CNVs larger than 1 megabase (P = .002) and including more than 10 genes (P = .005) occurred more frequently in patients than in control subjects. Nine patients (34.6%) among those harboring rare CNVs showed rearrangements associated with emerging microdeletion or microduplication syndromes. Mental retardation and neuropsychiatric features were associated with rare CNVs (P = .004), whereas epilepsy type was not. The CNV rate in patients with epilepsy and mental retardation or neuropsychiatric features is not different from that observed in patients with mental retardation only. Moreover, significant enrichment of genes involved in ion transport was observed within CNVs identified in patients with epilepsy. Conclusions Patients with epilepsy show a significantly increased burden of large, rare, gene-rich CNVs, particularly when associated with mental retardation and neuropsychiatric features. The limited overlap between CNVs observed in the epilepsy group and those observed in the group with mental retardation only as well as the involvement of specific (ion channel) genes indicate a specific association between the identified CNVs and epilepsy. Screening for CNVs should be performed for diagnostic purposes preferentially in patients with epilepsy and mental retardation or neuropsychiatric features.

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.

Cephalohematoma is a subperiosteal collection of blood above the skull. It is associated with operative and prolonged deliveries. In most cases the hematoma spontaneously resolves in a short span of time, usually within one month. In a few cases cephalohematoma can become ossified and require surgical treatment. Traditional belief that ossified cephalohematomas are an exclusively cosmetic issue has been called into question by recent description of EEG anomalies associated to a calcified cephalohematoma. We review relevant surgical literature, and we describe a novel variant of Wong's Radial Cap technique by foregoing healthy bone margin removal, removing the cephalohematoma lamellae in a stepwise fashion and using resorbable plaques for fixation. We furthermore review the rationale, timing and step-by-step execution of the procedure. An exemplary case description is discussed.

Chronic suppurative otitis media (CSOM) may result in a serious impairment of the quality of life (QoL). The most relevant characteristics of CSOM are well represented in the "Chronic Otitis Media Outcome Test 15" questionnaire (COMOT-15). The aim of the study was to translate and adapt the COMOT-15 questionnaire into Italian.This is a prospective study conducted on 52 Caucasian Italian-speaking patients with CSOM and 52 controls. The linguistic adaptation of the COMOT-15 consisted of the translation of the English version into Italian and reliability assessment of the translation. Psychometric measurements included internal consistency and test-retest reliability.Cronbach's α was 0.95. The test-retest reliability showed a strong positive correlation for total score and all subscales. Age and gender had no influence on the scores. The correlation between the COMOT-15 and the pure tone average showed a significant association for the scale "Hearing Function".The Italian COMOT-15 questionnaire provides good internal consistency and is suitable for QoL evaluation in Italian-speaking patients suffering from CSOM. In addition, it is able to evaluate the subjective symptoms perceived by patients.Adattamento culturale e validazione in italiano del questionario COMOT-15 nella valutazione degli outcomes del trattamento dell’otite media cronica.L’otite media cronica suppurativa (OMCS) può determinare una grave compromissione della qualità della vita (QoL) dei pazienti. Gli aspetti clinici più rilevanti dell’OMCS sono rappresentati nel questionario “Chronic Otitis Media Outcome Test 15” (COMOT-15). Scopo dello studio è tradurre e adattare alla lingua italiana il questionario COMOT-15.Abbiamo effettuato uno studio prospettico di validazione arruolando 52 pazienti con diagnosi di OMCS e 52 controlli. Il processo di adattamento linguistico del questionario è consistito nella traduzione della versione originale inglese in italiano e nella misura dell’affidabilità della stessa. Le misure psicometriche che abbiamo preso in considerazione includevano coerenza interna e affidabilità test-retest.Il Cronbach α era pari a 0,95. Abbiamo riscontrato una forte correlazione positiva sia per il punteggio totale che per tutte le sottoscale. Età e sesso non hanno influenzato i punteggi. L’analisi delle correlazioni tra COMOT-15 e soglia uditiva per la via aerea ha mostrato un’associazione significativa per la sottoscala “Funzione uditiva”.Sulla base dei nostri risultati è stato possibile dimostrare che la versione italiana del questionario COMOT-15 da noi proposta ha una buona coerenza interna ed è particolarmente adatta per la valutazione della QoL nei pazienti di lingua italiana affetti da otite media cronica suppurativa. Inoltre, esso è in grado di valutare i sintomi soggettivi percepiti dai pazienti.

Objective Germline BRCA1-2 pathogenic variants (gBRCApv) increase the risk of pancreatic cancer and predict for response to platinating agents and poly(ADP-ribose) polymerase inhibitors. Data on worldwide gBRCApv incidence among pancreatic ductal adenocarcinoma (PDAC) patients are sparse and describe a remarkable geographic heterogeneity. The aim of this study is to analyze the epidemiology of gBRCApv in Italian patients. Materials and methods Patients of any age with pancreatic adenocarcinoma, screened within 3 months from diagnosis for gBRCApv in Italian oncologic centers systematically performing tests without any selection. For the purposes of our analysis, breast, ovarian, pancreas, and prostate cancer in a patient's family history was considered as potentially BRCA-associated. Patients or disease characteristics were examined using the χ2 test or Fisher's exact test for qualitative variables and the Student's t-test or Mann–Whitney test for continuous variables, as appropriate. Results Between June 2015 and May 2020, 939 patients were tested by 14 Italian centers; 492 (52%) males, median age 62 years (range 28-87), 569 (61%) metastatic, 273 (29%) with a family history of potentially BRCA-associated cancers. gBRCA1-2pv were found in 76 patients (8.1%; 9.1% in metastatic; 6.4% in non-metastatic). The gBRCA2/gBRCA1 ratio was 5.4 : 1. Patients with gBRCApv were younger compared with wild-type (59 versus 62 years, P = 0.01). The gBRCApv rate was 17.1% among patients 70 years old (none out of 94 patients >73 years old). gBRCApv frequency in 845 patients, Highlights • This is the largest case series of incident PDAC patients screened for germline BRCA1-2 pathologic variants (gBRCApv). • The incidence of gBRCA1-2pv was 8.1% in the whole population; 9.1% in metastatic patients; 6.4% in non-metastatic patients. • No gBRCA1-2pv was observed over the age of 73. • These data suggest screening all PDAC patients

La sindrome da apnee notturne: correlazione con l’obesità e gestione del paziente obeso.La sindrome da apnee notturne è una malattia caratterizzata da ostruzione delle vie aeree superiori durante il sonno, abbastanza frequente nella popolazione generale, anche se sottovalutata. Russamenti, apnee notturne e ipersonnia diurna sono comuni in questi pazienti. L’obesità svolge un ruolo chiave: riduce le dimensioni e modifica la conformazione delle vie aeree superiori, oltre a prevenire l’espansione polmonare, con conseguente riduzione dei volumi polmonari. Le persone obese sono anche resistenti alla leptina, che stimola fisiologicamente la ventilazione; di conseguenza, questo provoca uno scarso risveglio durante l’apnea. La diagnosi si basa sulla combinazione di parametri clinici, come indice di apnea / ipopnea (AHI), anamnesi, valutazione clinica e Mallampati score. La prima indagine strumentale per identificare pazienti OSAHS è la polisonnografia seguita dalla sleep endoscopy. La terapia prevede in primo luogo la riduzione del peso corporeo, seguita dalla ventilazione a pressione positiva continua delle vie aeree (CPAP), che rimane ancora ad oggi il trattamento di scelta nella maggior parte dei pazienti, dispositivi di avanzamento mandibolare (MAD) e infine diversi approcci chirurgici. Tra le tecniche chirurgiche la faringoplastica (BRP), rappresenta la tecnica prescelta.Obstructive sleep apnoea/hypopnoea syndrome (OSAHS) is a disease characterised by upper airway obstruction during sleep, quite frequent in the general population, even if underestimated. Snoring, sleep apnoea and diurnal hypersomnia are common in these patients. Central obesity plays a key role: it reduces the size and changes the conformation of the upper airways, besides preventing lung expansion, with consequent reduction of lung volumes. Furthermore, obese people are also resistant to leptin, which physiologically stimulates ventilation; as a result, this causes scarce awakening during apnoea. OSAHS diagnosis is based on the combination of clinical parameters, such as apnoea/hypopnoea index (AHI), medical history, physical examination and Mallampati score. The first objective reference method to identify OSAHS is polysomnography followed by sleep endoscopy. Therapy provides in the first instance reduction of body weight, followed by continuous positive airway pressure (CPAP), which still remains the treatment of choice in most patients, mandibular advancement devices (MAD) and finally otolaryngology or maxillofacial surgery. Among surgical techniques, central is barbed reposition pharyngoplasty (BRP), used in the field of multilevel surgery.

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.

Case series Patients: Male, 74-year-old • Male, 76-year-old • Male, 77-year-old Final Diagnosis: Malignant otitis externa Symptoms: Edema • facial paralysis • hearing loss • otalgia and major otorrhea in the right ear Medication: — Clinical Procedure: ENT examination Specialty: Otolaryngology Objective: Unusual clinical course Background: Malignant external otitis (MEO) is an invasive infection that can involve the external auditory canal and the skull base up to the contiguous soft tissues. Considering the changing face of MEO, we reviewed cases of MEO treated in our Ear Nose Throat (ENT) clinic – University Federico II of Naples between 2018 and 2019 to evaluate the current epidemiology of the condition and to assess the state of art on diagnosis, therapeutic and follow-up management in our patients. Case Reports: We present the cases of three male patients with Type 2 diabetes mellitus who complained of long-lasting otorrhea and pain, with clinical suspicion of MEO. In all cases, ear swab was positive for Pseudomonas aeruginosa. All our patients received a 6-week course of intravenous ciprofloxacin, piperacillin, and tazobactam, with rapid clinical symptoms improvement and complete recovery at 1-year follow-up. Conclusions: MEO is difficult to treat due to the lack of standardized care guidelines. Patients with MEO often present with severe otalgia, edema, otorrhea, and facial nerve paralysis. Clinicians must suspect MEO in elderly diabetic and immunocompromised patients with persistent otalgia after external otitis. Imaging (computed tomography and magnetic resonance imaging) can play synergistic roles in the management of MEO. To evaluate eradication of the disease, clinicians have to assess clinical symptoms and signs as well as radiological imaging and inflammatory markers.

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.

Purpose To evaluate the effects of increased endogenous Antisecretory Factor (AF) synthesis using specially processed cereals (SPC) in a sample of patients with defined unilateral Meniere’s disease (MD), compared to the results of a treatment protocol of intravenous glycerol and dexamethasone. Materials and methods Twenty-six patients with unilateral MD were divided in 2 groups and treated with SPC and with intravenous glycerol and dexamethasone for 24 months. Audio-vestibular evaluation was performed before (T0) and every six months. The number of vertigo spells were evaluated before and after therapy and the Efficacy Index (EI) was calculated. Questionnaires for hearing loss, tinnitus and quality of life were administered. Results EI decreased in the SPC group after 18 (T18) (p = .0017) and 24 (T24) months of therapy (p = .0111). There was a significant reduction for tinnitus score in the SPC group at T24 (p = .0131). No significant differences were found between the two groups at T0 (p = .4723), while a significant difference was found at T24 (p = .0027). Quality of life showed a significant improvement in daily activities in the SPC group (p = .0033) compared to the infusion therapy group. No statistically significant changes in PTA thresholds were found in both groups between T0 and T24. Conclusion The preliminary results of our study show a significant reduction of vertigo spells and a positive effect on tinnitus severity and on quality of life in patients with unilateral MD treated with SPC and when compared to patients treated with intravenous glycerol and dexamethasone. No effects on hearing thresholds were noted in both groups.

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.

Purpose: Specially processed cereals (SPC) that increase endogenous antisecretory factor (AF) synthesis have been proposed to improve symptoms of Meniere’s disease (MD) with controversial results. The aim of this study was to evaluate the effects of SPC in patients with definite unilateral MD and compare the results to a treatment protocol with intravenous glycerol and dexamethasone. Methods: Thirteen patients with unilateral MD were treated with SPC and 13 patients were treated with intravenous glycerol and dexamethasone for 12 months. Audio-vestibular evaluation was performed before (T0) and at the end of the treatments (T12). The number of vertigo spells were evaluated before and after therapy and the Efficacy Index (EI) was calculated. Questionnaires for hearing loss (HHIA), tinnitus (THI) and quality of life (TFL) were administered. Results: EI decreased in the SPC group in the second semester compared to the first although not significantly (p = 0.6323). There was a significant reduction for THI score in the SPC group at T12 (p = 0.0325). No significant differences were found between the two groups at T0 (p = 0.4723), while a significant difference was found at T12 (p = 0.0041). Quality of life showed an improvement in daily activities in the SPC group compared to infusion therapy group. Conclusion: Our study shows a reduced number of vertigo attacks and a positive effect on the discomfort generated by tinnitus and quality of life in patients with unilateral MD treated with SPC and when compared to patients treated with intravenous glycerol and dexamethasone. No effects on hearing thresholds were noted in both groups.

Background: Vagus nerve stimulation (VNS) is a palliative treatment for medical intractable epileptic syndromes not eligible for resective surgery. Health technology assessment (HTA) represents a modern approach to the analysis of technologies used for healthcare. The purpose of this study is to assess the clinical, organizational, financial, and economic impact of VNS therapy in drug-resistant epilepsies and to establish the congruity between costs incurred and health service reimbursement. Methods: The present study used an HTA approach. It is based on an extensive detailed bibliographic search on databases (Medline, Pubmed, Embase and Cochrane, sites of scientific societies and institutional sites). The HTA study includes the following issues: (a) social impact and costs of the disease; (b) VNS eligibility and clinical results; (c) quality of life (QoL) after VNS therapy; (d) economic impact and productivity regained after VNS; and (e) costs of VNS. Results: Literature data indicate VNS as an effective treatment with a potential positive impact on social aspects and on quality of life. The diagnosis-related group (DRG) financing, both on national and regional levels, does not cover the cost of the medical device. There was an evident insufficient coverage of the DRG compared to the full cost of implanting the device. Conclusions: VNS is a palliative treatment for reducing seizure frequency and intensity. Despite its economic cost, VNS should improve patients’ quality of life and reduce care needs.

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.

Introduction: We described a rare clinical case of osteoma associated with homolateral radicular cyst of the maxillary sinus. Observation: Imaging showed two different lesions in the right maxillary sinus. We performed a combined surgical approach to completely remove the lesions and used a plasma rich in growth factors membrane to repair dental roots. No relapse after a 2 years follow-up was observed. Commentaries: The simultaneous presence of two large lesions, a 23,7 mm osteoma and a 33,7 mm radicular cyst in the same maxillary sinus, has been rarely described in the literature. Although nasal endoscopy and imaging are mandatory to assess the diagnosis, the definitive diagnosis was obtained after histopathologic examination. A combined surgical approach allowed a complete removal of both lesions, ensuring, at same time, an optimal surgical field. Plasma rich in growth factors membrane due to its cohesive properties was particularly useful in improving bone neoformation and periodontal regeneration. Conclusion: Diagnostic assessment of maxillary lesions requires nasal endoscopy, imaging and histopathological examination. If these lesions are symptomatic, they should be completely removed and minimally invasive surgery is indicated. Plasma rich in growth factors membrane ensures a good postoperative recovery.

Rubinstein–Taybi syndrome (RSTS) is a rare, clinically heterogeneous disorder characterized by cognitive impairment and several multiple congenital anomalies. The syndrome is caused by almost private point mutations in the CREBBP (~55% of cases) and EP300 (~8%) genes. The CREBBP mutational spectrum is variegated and characterized by point mutations (30–50%) and deletions (~10%). The latter are diverse in size and genomic position and remove either the whole CREBBP gene and its flanking regions or only an intragenic portion. Here, we report 14 novel CREBBP deletions ranging from single exons to the whole gene and flanking regions which were identified by applying complementary cytomolecular techniques: fluorescence in situ hybridization, multiplex ligation-dependent probe amplification and array comparative genome hybridization, to a large cohort of RSTS patients. Deletions involving CREBBP account for 23% of our detected CREBBP mutations, making an important contribution to the mutational spectrum. Genotype–phenotype correlations revealed that patients with CREBBP deletions extending beyond this gene did not always have a more severe phenotype than patients harboring CREBBP point mutations, suggesting that neighboring genes play only a limited role in the etiopathogenesis of CREBBP-centerd contiguous gene syndrome. Accordingly, the extent of the deletion is not predictive of the severity of the clinical phenotype.

Fumonisin B-1 (FB1) is a water-soluble fungal metabolite that elicits a wide spectrum of toxicological effects. Cellular targets of FB1 include immune cells and in particular macrophages. In the present study the cytotoxic effect of FB1 (1-100 muM) was evaluated using a murine macrophage cell line (J774A.1) as model system. The effect of FB1 on nitric oxide (NO) and prostaglandin E-2 (PGE(2)) production induced by lipopolysaccharide (LPS, 10 and 100 ng/ml) was also investigated. Macrophages were pretreated with FB1 for 72 h and then stimulated with LPS for 24 h. The increase of LPS-induced production of these inflammatory mediators was observed at increasing concentrations of FB1 (0.1-10 10 muM) and was found to be concentration dependent. By western blot analysis we demonstrated that the observed increase of NO and PGE(2) production by FB1 was related to an enhancement of iNOS and COX-2 expression.

The objective of this study was to evaluate hearing impairment in patients affected by Parkinson's disease compared with hearing scores observed in normal age- and sex-matched controls. One hundred eighteen consecutive patients with a clinical diagnosis of Parkinson's disease were screened. Severity of motor symptoms and staging were measured with the Unified Parkinson's Disease Rating Scale (section III) and the Hoehn and Yahr scale. Audiometric evaluation consisted of a comprehensive audiologic case history and questionnaire, visual otoscopic examination, acoustic immittance measures (tympanogram and acoustic reflexes), pure tone audiometry, and measurement of brain stem auditory-evoked potentials. Healthy age- and sex-matched subjects were selected as the control group. One hundred six of 118 patients were enrolled. Pure tone audiometry revealed age-dependent high-frequency hearing loss in patients with Parkinson's disease compared with both normative values and values for healthy age- and sex-matched controls (75/106 [71%], χ(2) = 5.959, P = .02; 92/106 [86.8%] vs 60/106 [56.6%], χ(2) = 23.804, P < .001, respectively). Pure tone audiometry scores correlated with Hoehn and Yahr scale scores (P < .05). Brain stem auditory-evoked potentials were normal in all patients. Our patients with Parkinson's disease showed age-dependent peripheral, unilateral, or bilateral hearing impairment. Whether these auditory deficits are intrinsic to Parkinson's disease or secondary to a more complex impaired processing of sensorial inputs occurring over the course of illness remains to be determined. Because α-synuclein is located predominately in the efferent neuronal system within the inner ear, it could affect susceptibility to noise-induced hearing loss or presbycusis. It is feasible that the natural aging process combined with neurodegenerative changes intrinsic to Parkinson's disease might interfere with cochlear transduction mechanisms, thus anticipating presbycusis.

To determine the benefit of nasally inhaled dornase alfa in patients with cystic fibrosis and nasal symptoms.Double-blind placebo-controlled trial.Cystic Fibrosis Regional Center of Campania at the University of Naples "Federico II."A total of 24 patients with cystic fibrosis and chronic sinusitis.Patients underwent sinonasal surgery during a 3-year period and received once-daily doses of either dornase alfa (2.5 mg) or hypotonic saline solution (5 mL) beginning 1 month after surgery and for a 12-month period.Primary outcomes were nasal-related symptoms and nasal endoscopic appearance; secondary outcomes were forced expiratory volume in 1 second, nasal computed tomography findings, and saccharine clearance test results. Patients were evaluated before and after treatment.After surgery, all outcomes were significantly improved for each treatment at 1 month (P.05); primary outcomes were improved at 24 and 48 weeks in the group receiving dornase alfa (P.05), and at 12 weeks in the group receiving placebo. Secondary outcomes were better in the dornase alfa group (P.01) than in the placebo group at 12 months except for the saccharine clearance test results. In particular, median relative difference in forced expiratory volume in 1 second between dornase alfa and placebo was significantly improved in the dornase alfa group (P.01).Nasally inhaled dornase alfa can be effective in patients with cystic fibrosis and sinonasal disease who do not respond to conventional therapy after surgical treatment. Further studies should be carried out to determine the long-term effect on sinus disease, recurrence of polyps, and quality of life.

Background: Cystic fibrosis (CF) airways are characterised by chronic inflammation, increased interleukin (IL)-8 secretion, and neutrophil activation which are considered the principal factors of morbidity and mortality in CF patients. Optimising management of this chronic inflammatory response is therefore a key issue of basic and clinical CF research. Several reports have addressed ways to manage CF airways inflammation, and an attractive therapeutic strategy may be the inhibition of the p38-mitogen activated protein kinase (p38-MAP-k) pathway. Methods: A new ex vivo model was used to study the mucosal inflammatory response to environmental airways stimuli. Nasal biopsy tissues from CF patients and controls were cultured ex vivo for 20 minutes, 4 hours, and 24 hours in the presence of lipopolysaccharide (LPS) from Pseudomonas aeruginosa (PA) with and without the p38-MAP-k inhibitor SB203580. Quantitative mRNA assessment, immunohistochemistry, and Western blots were used to detect the expression and modulation of inflammatory markers. Results: PA-LPS challenge induced a time dependent mucosal inflammation indicated by rapid epithelial activation, IL-8 release, COX-2 upregulation, and neutrophil migration to the upper mucosal layers. Some of these LPS induced changes (IL-8 release and neutrophil migration) were specific to CF tissues. SB203580 significantly controlled all LPS induced mucosal changes in CF tissues. Conclusion: These findings provide a rationale and proof of principle for the potential use of p38-MAP-k inhibitors to control inflammation in patients with CF.