Targeting irradiation-induced mitogen-activated protein kinase activation in vitro and in an ex vivo model for human head and neck cancer.

Targeting irradiation-induced mitogen-activated protein kinase activation in vitro and in an ex vivo model for human head and neck cancer.

Head Neck. 2016 Feb 26;

Authors: Affolter A, Muller MF, Sommer K, Stenzinger A, Zaoui K, Lorenz K, Wolf T, Sharma S, Wolf J, Perner S, Weber KJ, Freier K, Plinkert PK, Hess J, Weichert W

Abstract
BACKGROUND: Despite new radiotherapeutic strategies, radioresistance in head and neck squamous cell carcinoma (HNSCC) remains a major problem. Preclinical model systems are needed to identify resistance mechanisms in this heterogeneous entity.
METHODS: We elucidated the interplay among mitogen-activated protein kinase (MAPK)-inhibition, radiation, and p53 mutations in vitro and in a novel ex vivo model derived from vital human HNSCC samples. HNSCC cell lines (p53WT/mut) were treated with the mitogen-activated protein kinase (MEK)-inhibitor PD-0325901 and subsequently irradiated. Radiosensitization was functionally assessed and evaluated in the ex vivo model.
RESULTS: We observed a pronounced irradiation-induced extracellular signal-regulated kinase (ERK) phosphorylation in 2 cell lines, which was independent of their p53 mutation status and associated with PD-0325901-related radiosensitization in a clonogenic assay. Heterogeneity in irradiation-induced ERK phosphorylation and in radiosensitization after MEK-inhibition was also reflected in the ex vivo model.
CONCLUSION: We provide experimental evidence for radiosensitizing effects of PD-0325901 in HNSCC. The ex vivo culture technology might offer a promising tool for individualized drug efficacy testing. © 2016 Wiley Periodicals, Inc. Head Neck, 2016.

PMID: 26918677 [PubMed - as supplied by publisher]

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Phase II study of erlotinib and docetaxel with concurrent intensity-modulated radiotherapy in locally advanced head and neck squamous cell carcinoma.

Phase II study of erlotinib and docetaxel with concurrent intensity-modulated radiotherapy in locally advanced head and neck squamous cell carcinoma.

Head Neck. 2016 Feb 26;

Authors: Yao M, Woods C, Lavertu P, Fu P, Gibson M, Rezaee R, Zender C, Wasman J, Sharma N, Machtay M, Savvides P

Abstract
BACKGROUND: The purpose of this study was to establish the efficacy and toxicities of concurrent erlotinib and docetaxel with intensity-modulated radiotherapy (IMRT) for locally advanced head and neck squamous cell carcinoma (HNSCC).
METHODS: Patients received daily erlotinib for 2 weeks, followed by daily IMRT with concurrent weekly docetaxel and daily erlotinib, followed by daily erlotinib for up to 2 years. The primary objective was disease-free survival (DFS). Secondary objectives included overall survival (OS), patterns of failure, and toxicities. Forty-three patients were recruited for this study.
RESULTS: With a median follow-up of 48.7 months, the 3-year DFS, OS, locoregional failure-free survival, and distant metastasis-free survival was 69.5%, 81%, 82.4%, and 83.7%, respectively. The most common grade III/IV local toxicities were dysphagia, dermatitis, and mucositis. Patients with p16-positive tumors had significantly better outcomes.
CONCLUSION: The regimen is tolerable and effective. It is worthy of further investigation in selected patients and may be useful in patients who cannot tolerate cisplatin. © 2016 Wiley Periodicals, Inc. Head Neck, 2016.

PMID: 26918562 [PubMed - as supplied by publisher]

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Cerebral Processing of Emotionally Loaded Acoustic Signals by Tinnitus Patients.

Cerebral Processing of Emotionally Loaded Acoustic Signals by Tinnitus Patients.

Audiol Neurootol. 2016 Feb 27;21(2):80-87

Authors: Georgiewa P, Szczepek AJ, Rose M, Klapp BF, Mazurek B

Abstract
This exploratory study determined the activation pattern in nonauditory brain areas in response to acoustic, emotionally positive, negative or neutral stimuli presented to tinnitus patients and control subjects. Ten patients with chronic tinnitus and without measurable hearing loss and 13 matched control subjects were included in the study and subjected to fMRI with a 1.5-tesla scanner. During the scanning procedure, acoustic stimuli of different emotional value were presented to the subjects. Statistical analyses were performed using statistical parametric mapping (SPM 99). The activation pattern induced by emotionally loaded acoustic stimuli differed significantly within and between both groups tested, depending on the kind of stimuli used. Within-group differences included the limbic system, prefrontal regions, temporal association cortices and striatal regions. Tinnitus patients had a pronounced involvement of limbic regions involved in the processing of chimes (positive stimulus) and neutral words (neutral stimulus), strongly suggesting improperly functioning inhibitory mechanisms that were functioning well in the control subjects. This study supports the hypothesis about the existence of a tinnitus-specific brain network. Such a network could respond to any acoustic stimuli by activating limbic areas involved in stress reactivity and emotional processing and by reducing activation of areas responsible for attention and acoustic filtering (thalamus, frontal regions), possibly reinforcing negative effects of tinnitus.

PMID: 26918795 [PubMed - as supplied by publisher]

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Progression of unilateral moyamoya disease resulted in spontaneous occlusion of ipsilateral cavernous dural arteriovenous fistula: Case report.

Progression of unilateral moyamoya disease resulted in spontaneous occlusion of ipsilateral cavernous dural arteriovenous fistula: Case report.

Interv Neuroradiol. 2016 Feb 24;

Authors: Liu P, Xu Y, Lv X, Ge H, Lv M, Li Y

Abstract
The pathogenic association between cavernous dural arteriovenous fistula (CDAVF) and moyamoya disease remains unclear. This unusual case is the first report of a progression of unilateral moyamoya disease resulting in the spontaneous occlusion of ipsilateral CDAVF. A 52-year-old woman presented with two-week spontaneous exophthalmos, chemosis and tinnitus, and cerebral angiography showed a right CDAVF coexisting with ipsilateral moyamoya disease. Transvenous approaches through the inferior petrosal sinus and facial vein were attempted but failed. However, a progression of the moyamoya disease and disappearance of the CDAVF were observed on one month follow-up angiogram in accordance with the resolution of clinical symptoms. This extremely rare coincidental presentation may have deeper pathogenic implications. This case report may give a clue to the underlying mechanism of the progression of moyamoya disease and occlusion of the CDAVF.

PMID: 26916656 [PubMed - as supplied by publisher]

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Racial differences in vestibular schwannoma.

Racial differences in vestibular schwannoma.

Laryngoscope. 2016 Feb 24;

Authors: Carlson ML, Marston AP, Glasgow AE, Habermann EB, Sweeney AD, Link MJ, Wanna GB

Abstract
OBJECTIVES/HYPOTHESIS: To estimate the impact of race on disease presentation and treatment of vestibular schwannoma (VS) in the United States.
STUDY DESIGN: Analysis of a national population-based tumor registry.
METHODS: Analysis of the Surveillance, Epidemiology, and End Results database was performed, including all patients identified with a diagnosis of VS. Associations between race, disease presentation, treatment strategy, and overall survival were analyzed in a univariate and multivariable model.
RESULTS: A total of 9,782 patients with VS were identified among 822 million person-years. Of these, 7,400 (75.6%) claimed white, 807 (8.2%) Hispanic, 755 (7.7%) Asian, 397 (4.1%) black, and 423 (4.3%) patients reported other race. The median annual incidence of disease was lowest among black (0.43 per 100,000 persons) and Hispanic populations (0.45 per 100,000 persons) and highest among white (1.61 per 100,000 persons) populations (P < 0.001). Overall, Hispanic patients were diagnosed at the youngest age, and white patients were diagnosed at the oldest age (mean of 50.0 vs. 56.0 years, respectively; P < 0.001). Compared to white populations, black, Hispanic, and Asian populations were more likely to present with larger tumors (P < 0.001). After controlling for tumor size, age, and treatment center in a multivariable model, Hispanic patients were more likely than white patients to undergo surgery (P = 0.010); however, there were no differences between white, black, and Asian populations with regard to treatment modality. Hispanic and black patients had the poorest overall survival following surgery compared to other groups.
CONCLUSION: Racial differences among patients with VS exist within the United States. Further studies are required to determine which factors drive differences in tumor size, age, annual disease incidence, and overall survival between races.
LEVEL OF EVIDENCE: 3. Laryngoscope, 2015.

PMID: 26917495 [PubMed - as supplied by publisher]

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Risk of post-operative pneumocephalus in patients with obstructive sleep apnea undergoing transsphenoidal surgery.

Risk of post-operative pneumocephalus in patients with obstructive sleep apnea undergoing transsphenoidal surgery.

J Clin Neurosci. 2016 Feb 22;

Authors: White-Dzuro GA, Maynard K, Zuckerman SL, Weaver KD, Russell PT, Clavenna MJ, Chambless LB

Abstract
Patients undergoing transsphenoidal surgery (TSS) have an anterior skull base defect that limits the use of positive pressure ventilation post-operatively. Obstructive sleep apnea (OSA) can be seen in these patients and is treated with continuous positive airway pressure (CPAP). In our study we documented the incidence of pre-existing OSA and reported the incidence of diagnosed pneumocephalus and its relationship to OSA. A retrospective review was conducted from a surgical outcomes database. Electronic medical records were reviewed, with an emphasis on diagnosis of OSA and documented symptomatic pneumocephalus. A total of 324 patients underwent 349 TSS for sellar mass resection. The average body mass index of the study cohort was 32.5kg/m(2). Sixty-nine patients (21%) had documented OSA. Only 25 out of 69 (36%) had a documented post-operative CPAP plan. Out of all 349 procedures, there were two incidents of pneumocephalus diagnosed. Neither of the patients had pre-existing OSA. One in five patients in our study had pre-existing OSA. Most patients returned to CPAP use within several weeks of TSS for resection of a sellar mass. Neither of the patients with pneumocephalus had pre-existing OSA and none of the patients with early re-initiation of CPAP developed this complication. This study provides preliminary evidence that resuming CPAP early in the post-operative period might be less dangerous than previously assumed.

PMID: 26916903 [PubMed - as supplied by publisher]

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Functions of the inner ear in psoriatic arthritis.

Functions of the inner ear in psoriatic arthritis.

Auris Nasus Larynx. 2016 Feb 22;

Authors: Gunes A, Gundogdu I, Mutlu M, Ozturk EA, Cakci A, Akin I

Abstract
OBJECTIVE: This study aimed to investigate whether there is a negative impact as a result of psoriatic arthritis disease of the inner ear function.
METHODS: Twenty-four successive patients and 38 healthy volunteers, younger than 60 years of age, who were followed up for at least for one year in the outpatient clinics of physical therapy and rehabilitation with the diagnosis of PsA according to CASPAR criteria (17) and who did not complain of any hearing impairment were included in the study. Distortion-product otoacoustic emission (DPOAE) values between 1kHz and 4kHz, tympanometric examination results, stapes reflex values, speech reception threshold (SRT) and speech discrimination (SD) values, pure-tone values between 250 and 8000Hz and high-frequency values between 10,000, 12,500 and 16,000Hz were analyzed. Statistical comparisons between both groups were performed using chi-square test and Mann-Whitney U test. p<0.05 was accepted as the level of statistical significance.
RESULTS: Our study population consisted of 24 [9 male (37.5%) and 15 female (62.5%)] patients with a mean age of 47.21±11.28 (range, 28-59) years and 38 [16 male (42.1%) and 22 female (57.9%)] healthy volunteers with a mean age of 44.39±8.12 (range, 29-59) years as the control group. Mean duration of arthritis was 7.62±4.88 years. In the evaluation of hearing frequencies of the patients between 4000 and 6000Hz, a statistically significant difference was found relative to the control group (p<005). DPOAE values of the patients were analyzed within the 1000-4000Hz interval. When compared with the control group, a statistically significant difference was found at 3000 and 4000Hz (p<005).
CONCLUSION: Our study provides strong evidence suggesting the necessity of monitorization of these patients regarding sensorineural hearing loss so as to take measures against the development of hearing loss during early stage, which may be another disability in patients with PsA, which is itself a potential cause of severe disability.

PMID: 26915283 [PubMed - as supplied by publisher]

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Motivational engagement in first-time hearing aid users: A feasibility study.

Motivational engagement in first-time hearing aid users: A feasibility study.

Int J Audiol. 2016 Feb 26;:1-11

Authors: Ferguson M, Maidment D, Russell N, Gregory M, Nicholson R

Abstract
OBJECTIVE: To assess (1) the feasibility of incorporating the Ida Institute's Motivation Tools into a UK audiology service, (2) the potential benefits of motivational engagement in first-time hearing aid users, and (3) predictors of hearing aid and general health outcome measures.
DESIGN: A feasibility study using a single-centre, prospective, quasi-randomized controlled design with two arms. The Ida Institute's Motivation Tools formed the basis for motivational engagement.
STUDY SAMPLE: First-time hearing aid users were recruited at the initial hearing assessment appointment. The intervention arm underwent motivational engagement (M+, n = 32), and a control arm (M-, n = 36) received standard care only.
RESULTS: The M+ group showed greater self-efficacy, reduced anxiety, and greater engagement with the audiologist at assessment and fitting appointments. However, there were no significant between-group differences 10-weeks post-fitting. Hearing-related communication scores predicted anxiety, and social isolation scores predicted depression for the M+ group. Readiness to address hearing difficulties predicted hearing aid outcomes for the M- group. Hearing sensitivity was not a predictor of outcomes.
CONCLUSIONS: There were some positive results from motivational engagement early in the patient journey. Future research should consider using qualitative methods to explore whether there are longer-term benefits of motivational engagement in hearing aid users.

PMID: 26919044 [PubMed - as supplied by publisher]

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The case for earlier cochlear implantation in postlingually deaf adults.

The case for earlier cochlear implantation in postlingually deaf adults.

Int J Audiol. 2016 Feb 26;:1-6

Authors: Dowell RC

Abstract
OBJECTIVE: This paper aimed to estimate the difference in speech perception outcomes that may occur due to timing of cochlear implantation in relation to the progression of hearing loss.
DESIGN: Data from a large population-based sample of adults with acquired hearing loss using cochlear implants (CIs) was used to estimate the effects of duration of hearing loss, age, and pre-implant auditory skills on outcomes for a hypothetical standard patient.
STUDY SAMPLE: A total of 310 adults with acquired severe/profound bilateral hearing loss who received a CI in Melbourne, Australia between 1994 and 2006 provided the speech perception data and demographic information to derive regression equations for estimating CI outcomes.
RESULTS: For a hypothetical CI candidate with progressive sensorineural hearing loss, the estimates of speech perception scores following cochlear implantation are significantly better if implantation occurs relatively soon after onset of severe hearing loss and before the loss of all functional auditory skills.
CONCLUSIONS: Improved CI outcomes and quality of life benefit may be achieved for adults with progressive severe hearing loss if they are implanted earlier in the progression of the pathology.

PMID: 26918896 [PubMed - as supplied by publisher]

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Exploration of a physiologically-inspired hearing-aid algorithm using a computer model mimicking impaired hearing.

Exploration of a physiologically-inspired hearing-aid algorithm using a computer model mimicking impaired hearing.

Int J Audiol. 2016 Feb 26;:1-12

Authors: Jürgens T, Clark NR, Lecluyse W, Meddis R

Abstract
OBJECTIVE: To use a computer model of impaired hearing to explore the effects of a physiologically-inspired hearing-aid algorithm on a range of psychoacoustic measures.
DESIGN: A computer model of a hypothetical impaired listener's hearing was constructed by adjusting parameters of a computer model of normal hearing. Absolute thresholds, estimates of compression, and frequency selectivity (summarized to a hearing profile) were assessed using this model with and without pre-processing the stimuli by a hearing-aid algorithm. The influence of different settings of the algorithm on the impaired profile was investigated. To validate the model predictions, the effect of the algorithm on hearing profiles of human impaired listeners was measured.
STUDY SAMPLE: A computer model simulating impaired hearing (total absence of basilar membrane compression) was used, and three hearing-impaired listeners participated.
RESULTS: The hearing profiles of the model and the listeners showed substantial changes when the test stimuli were pre-processed by the hearing-aid algorithm. These changes consisted of lower absolute thresholds, steeper temporal masking curves, and sharper psychophysical tuning curves.
CONCLUSION: The hearing-aid algorithm affected the impaired hearing profile of the model to approximate a normal hearing profile. Qualitatively similar results were found with the impaired listeners' hearing profiles.

PMID: 26918797 [PubMed - as supplied by publisher]

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Safety of epidural triamcinolone acetonide use during lumbar decompression surgery in pediatric patients: an association with delayed pseudomeningocele formation.

Safety of epidural triamcinolone acetonide use during lumbar decompression surgery in pediatric patients: an association with delayed pseudomeningocele formation.

J Neurosurg Pediatr. 2016 Feb 26;:1-5

Authors: Sellin JN, Vedantam A, Luerssen TG, Jea A

Abstract
OBJECTIVE The complication profile of epidural triamcinolone acetonide use during lumbar decompression surgery is not known. However, isolated reports of increased risk of delayed CSF leakage with the use of triamcinolone acetonide in adult spinal surgery patients have been published. The purpose of this study was to determine the safety of epidural triamcinolone acetonide use in conjunction with lumbar decompression surgery in pediatric patients. METHODS The medical records of all patients who underwent lumbar decompression surgery with or without discectomy between July 1, 2007, and July 31, 2015, were retrospectively reviewed. RESULTS During the study period, 58 patients underwent 59 spine procedures at Texas Children's Hospital. There were 33 female and 25 male patients. The mean age at surgery was 16.5 years (range 12-24 years). Patients were followed for an average of 38.2 months (range 4-97 months). Triamcinolone acetonide was used in 28 (of 35 total) cases of discectomy; there were no cases of delayed symptomatic CSF leaks (0%) in the minimally invasive and open discectomies. On the other hand, triamcinolone acetonide was used in 14 (of 24 total) cases of multilevel laminectomy, among which there were 10 delayed CSF leaks (71.4%) requiring treatment. The use of triamcinolone acetonide in patients who underwent multilevel laminectomy was significantly associated with an increased risk of delayed CSF leaks or pseudomeningoceles (Fisher's exact test, p < 0.001). CONCLUSIONS There was an unacceptable incidence of delayed postoperative CSF leaks when epidural triamcinolone acetonide was used in patients who underwent multilevel laminectomy.

PMID: 26919317 [PubMed - as supplied by publisher]

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