A test for Creutzfeldt-Jakob disease using nasal brushings.

BACKGROUND: Definite diagnosis of sporadic Creutzfeldt-Jakob disease in living patients remains a challenge. A test that detects the specific marker for Creutzfeldt-Jakob disease, the prion protein (PrP(CJD)), by means of real-time quaking-induced conversion (RT-QuIC) testing of cerebrospinal fluid has a sensitivity of 80 to 90% for the diagnosis of sporadic Creutzfeldt-Jakob disease. We have assessed the accuracy of RT-QuIC analysis of nasal brushings from olfactory epithelium in diagnosing sporadic Creutzfeldt-Jakob disease in living patients. METHODS: We collected olfactory epithelium brushings and cerebrospinal fluid samples from patients with and patients without sporadic Creutzfeldt-Jakob disease and tested them using RT-QuIC, an ultrasensitive, multiwell plate-based fluorescence assay involving PrP(CJD)-seeded polymerization of recombinant PrP into amyloid fibrils. RESULTS: The RT-QuIC assays seeded with nasal brushings were positive in 30 of 31 patients with Creutzfeldt-Jakob disease (15 of 15 with definite sporadic Creutzfeldt-Jakob disease, 13 of 14 with probable sporadic Creutzfeldt-Jakob disease, and 2 of 2 with inherited Creutzfeldt-Jakob disease) but were negative in 43 of 43 patients without Creutzfeldt-Jakob disease, indicating a sensitivity of 97% (95% confidence interval [CI], 82 to 100) and specificity of 100% (95% CI, 90 to 100) for the detection of Creutzfeldt-Jakob disease. By comparison, testing of cerebrospinal fluid samples from the same group of patients had a sensitivity of 77% (95% CI, 57 to 89) and a specificity of 100% (95% CI, 90 to 100). Nasal brushings elicited stronger and faster RT-QuIC responses than cerebrospinal fluid (P<0.001 for the between-group comparison of strength of response). Individual brushings contained approximately 10(5) to 10(7) prion seeds, at concentrations several logs10 greater than in cerebrospinal fluid. CONCLUSIONS: In this preliminary study, RT-QuIC testing of olfactory epithelium samples obtained from nasal brushings was accurate in diagnosing Creutzfeldt-Jakob disease and indicated substantial prion seeding activity lining the nasal vault. (Funded by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases and others.).

Jawbone fibrous dysplasia: retrospective evaluation in a cases series surgically treated and short review of the literature.

BACKGROUND AND AIM OF THE WORK: Fibrous dysplasia is a fibro-osseous osteopathy in which the normal bone architecture is replaced by fibrous tissue and non-functional trabeculae-like osseous structures. In head and neck area monostotic or polyostotic lesions cause a progressively expanding destructive bone swelling producing cosmetic deformities and functional impairments. The aim of this article is to present a retrospective review of a clinical case series with pathologically confirmed jawbone fibrous dysplasia for over an 8-year-period. MATERIAL AND METHODS: Clinical presentation and radiographic features of fibrous dysplasia affecting the jawbone skeletal area, surgical procedures performed including the reconstructive methods employed and clinical outcomes were analysed for each patient. RESULTS: Seven cases were classified as having monostotic fibrous dysplasia while the others four cases were classified as having polyostotic form. The mandible was most commonly involved. The most common presenting features included marked facial deformity, intraoral bulging, malocclusion and dental alterations. Aesthetic and/or functional impairments were the major indications for surgical treatment in all the patients of this series. Six patients underwent bone remodelling while in the remaining cases subtotal or total resection was performed. Bone reconstruction by means of autologous free bone grafts or revascularized free bone flaps was made in three cases. CONCLUSION: The choice of the tailored therapeutic approach should be evaluated according the patient's age, rate of growth, anatomic location, type of involvement and the presence or not of functional disturbances and cosmetic alterations. Surgery remains the best therapeutic option.

[Clinical and histological latero-cervical nodal metastases in squamous oropharyngeal carcinoma]. / Metastasi laterocervicali nelle neoplasie squamose del distretto orofaringeo.

The goal of our study was to estimate the presence (or absence) of latero-cervical nodal metastases (pN+), in patients with squamous oropharyngeal cancer, correlating this finding with T stage. We examined 255 patients out of 329 affected by squamous oropharyngeal cancer, from 1976 to 2005. The 255 patients examined were treated surgically (both T and N). As far as clinical latero-cervical nodal metastases were concerned, 215 patients (84%) were cN+, while 40% (16%) were cN-. The result of the histological examination showed that 82% of the neck dissections (both cN+ and cN-) actually had latero-cervical metastases, while the remaining patients had reactive lymph nodes. The false-positive (cN+ -->pN-) patients, were 14% while false-negative patients (cN- -->pN+) amounted to 63%. The correlation between T and pN+ of the patients classified as cN- showed that 24% of patients were T1, 44% T2, 32% T3, and none T4; the pN+ patients, who clinically manifested latero-cervical lymph-node metastases were: T1 8%, T2 15%, T3 37%, T4 40%. Analysis of these data led us to the conclusion that, in view of the high lymphophilia of squamous cancer in the oropharyngeal district, it would be advisable to treat N metastases, both cN+ and cN-, at any T stage of cancer, surgically or with chemo- or radiotherapy, according to the patient's performance status.

The watch-pat in pediatrics sleep disordered breathing: Pilot study on children with negative nocturnal pulse oximetry.

OBJECTIVES: The main purpose of this study was to determine the efficacy of Watch-PAT in Pediatric Sleep Disordered Breathing (PSDB) diagnosis in children with symptoms suggestive of PSDB, in which the nocturnal pulse oximetry was negative according to the Brouilette criteria. METHODS: We enrolled 28 patients aged between 5 and 12 years (mean age: 7.75 ± 1.69), who underwent the registration with Watch-PAT, that utilizes the Peripheral Arterial Tone (PAT), AHI, RDI, body position, snoring, pulse oximetry and actigraphy. RESULTS: Recording Watch-PAT was indicative of PSDB in 10/28 (35.7%) patients; when it was placed the threshold of AHI > 1 the number of positive patients for PSDB increased to 17/28 (60.7%). Exists a positive correlation between pat-RDI (rho = 0.798, p = 0.005) and the snoring > 40% of the time (rho = 0.656, p < 0.001) were correlated with the pat-AHI values. CONCLUSION: The recording Watch-PAT appears to permit the defection of a certain number of SDB that might escape to the clinical evaluation and pulse oximetry only.

Multicenter research into the quality of life of patients with advanced oropharyngeal carcinoma with long-term survival associated with human papilloma virus.

The treatment of advanced-stage oropharyngeal squamous cell carcinoma may utilize various modes, including combining surgery with chemoradiotherapy (CTRT), or primary CTRT followed by rescue surgery. In previous literature it has been revealed how patients treated with combined modes report a low quality of life (QoL) and severe consequences following surgery, radiotherapy and chemotherapy, in the short and in the long-term. The decrease in the QoL of patients treated with high-intensity multi-modal strategies highlights the necessity of modifying treatments, particularly for young HPV-positive patients, where an increased survival rate has already been reported. The modified treatment for HPV-positive tumors in the tonsils and at the base of the tongue is based on the deintensification of therapies aiming to reduce toxicity and thereby improve QoL in the long term, whilst still maintaining therapeutic effectiveness. The aim of the present study was to evaluate the QoL in patients with a long-term survival, who were treated with combined therapy for squamous cell tumors in the tonsils and at the base of the tongue, and to compare the results observed in HPV-positive and HPV-negative patients. According to statistical analysis, differences in the general QoL and in the single scales of the European Organization for the Research and Treatment of Cancer questionnaires were not correlated with the type of therapy selected for the particular patient. QoL considered the presence of HPV, the type of treatment, the subregion of the tonsils vs. the base of the tongue and the disease stage at the time of diagnosis, and was determined to be non-influential with regard to these specific variables.

Diagnosis of Human Prion Disease Using Real-Time Quaking-Induced Conversion Testing of Olfactory Mucosa and Cerebrospinal Fluid Samples.

Importance: Early and accurate in vivo diagnosis of Creutzfeldt-Jakob disease (CJD) is necessary for quickly distinguishing treatable from untreatable rapidly progressive dementias and for future therapeutic trials. This early diagnosis is becoming possible using the real-time quaking-induced conversion (RT-QuIC) seeding assay, which detects minute amounts of the disease-specific pathologic prion protein in cerebrospinal fluid (CSF) or olfactory mucosa (OM) samples. Objective: To develop an algorithm for accurate and early diagnosis of CJD by using the RT-QuIC assay on CSF samples, OM samples, or both. Design, Setting, and Participants: In this case-control study, samples of CSF and OM were collected from 86 patients with a clinical diagnosis of probable (n = 51), possible (n = 24), or suspected (n = 11) CJD and 104 negative control samples (54 CSF and 50 OM). The CSF and OM samples were analyzed using conventional RT-QuIC. The CSF samples underwent further testing using improved RT-QuIC conditions. In addition, the diagnostic performance of a novel, easy-to-use, gentle flocked swab for sampling of OM was evaluated. Data were collected from January 1 to June 30, 2015. Main Outcome and Measures: Correlations between RT-QuIC results and the final diagnosis of recruited patients. Results: Among the 86 patients (37 men [43%] and 49 women [57%]; mean [SD] age, 65.7 [11.5] years) included for analysis, all 61 patients with sporadic CJD had positive RT-QuIC findings using OM or CSF samples or both for an overall RT-QuIC diagnostic sensitivity of 100% (95% CI, 93%-100%). All patients with a final diagnosis of non-prion disease (71 CSF and 67 OM samples) had negative RT-QuIC findings for 100% specificity (95% CI, 94%-100%). Of 8 symptomatic patients with various mutations causing CJD or Gerstmann-Sträussler-Scheinker syndrome, 6 had positive and 2 had negative RT-QuIC findings for a sensitivity of 75% (95% CI, 36%-96%). Conclusions and Relevance: A proposed diagnostic algorithm for sporadic CJD combines CSF and OM RT-QuIC testing to provide virtually 100% diagnostic sensitivity and specificity in the clinical phase of the disease.

Electrocochleography during cochlear implantation for hearing preservation.

OBJECTIVE: To determine whether intraoperative electrocochleography during cochlear implant surgery provides online feedback to modify surgical procedure, reduce trauma, and increase preservation of residual hearing. STUDY DESIGN: Prospective cohort study. SETTING: Tertiary referral center, Otolaryngology Department, University of Verona. SUBJECTS AND METHODS: Twenty-seven adult patients undergoing cochlear implant surgery who had low- to mid-frequency (0.25-2 kHz) auditory thresholds measured preoperatively were enrolled. Fifteen subjects had compound action potentials measured to assess cochlear function during surgery. In those patients, surgery was modified according to electrocochleographic feedback. Twelve control subjects underwent cochlear implant surgery with blinded electrocochleographic monitoring. RESULTS: The average preoperative pure-tone audiometry thresholds (0.25-2 kHz) were 74.3 ± 10.2 and 81.5 ± 12.7 dB hearing level (HL) in the electrocochleographic feedback and control cohorts, respectively (P > .05). Compound action potential recordings showed a mean maximum latency shift of 0.63 ± 0.36 ms and normalized amplitude deterioration of 59% ± 19% during surgery. All of these changes reverted to normal after electrode insertion in all but 1 subject in the electrocochleographic feedback group. The average shifts in postoperative pure-tone average threshold (0.25-2 kHz), evaluated before activation, were 8.7 ± 4.3 and 19.2 ± 11.4 dB HL in the electrocochleographic feedback and control cohorts, respectively (P = .0051). Complete hearing preservation (loss of ≤10 dB) at 1 month before activation was achieved in 85% (11/13) of electrocochleographic feedback subjects and in 33% (4/12) of control patients (P = .0154). CONCLUSION: Monitoring cochlear function with electrocochleography gives real-time feedback during surgery, providing objective data that might help in modifying the surgical technique in ways that can improve the rate of hearing preservation.