Prostate cancer screening by prostate-specific antigen (PSA); a relevant approach for the small population of the Cayman Islands

Abstract

Introduction

The common tool for diagnosing prostate cancer is prostate-specific antigen (PSA), but the high sensitivity and low specificity of PSA testing are the problems in clinical practice. There are no proper guidelines to investigate the suspected prostate cancer in the Cayman Islands. We correlated PSA levels with the incidence of prostate cancers by tissue diagnosis and proposed logical protocol for prostate screening by using PSA test in this small population.

Materials and methods

A total of 165 Afro Caribbean individuals who had prostate biopsy done after the investigations for PSA levels from year 2005 to 2015 were studied retrospectively. The patients were divided into subgroups by baseline PSA levels as follows: <4, 4.1–10, 10.1–20, 20.1–50, 50.1–100, and >100 ng/mL and were correlated to the age and presence of cancer.

Results and discussion

Benign lesions had lower PSA levels compared to cancer which generally had higher values. Only three cases that had less than 4 ng/mg were turned out to be malignant. When PSA value was more than 100 ng/mL, all the cases were malignant. Between PSA values of 4–100 ng/mL, the probability of cancer diagnosis was 56.71% (76 cancers out of 134 in this range). Limitation of PSA testing has the risk of over diagnosis and the resultant negative biopsies owing to poor specificity. Whereas the cutoff limit for cancer diagnosis still remains 4 ng/mL from our study, most of the patients can be assured of benign lesion below this level and thus morbidity associated with the biopsy can be prevented. When the PSA value is greater than 100 ng, biopsy procedure was mandatory as there were 100% cancers above this level.

Summary

On the background of vast literature linking PSA to prostate cancer and its difficulty in implementing in clinical practice, we studied literature of this conflicting and complex topic and tried to bring relevant protocols to the small population of Cayman Islands for the screening of prostate cancer. In this study, a total of 165 Afro Caribbean individuals who had prostate biopsy done after the investigations for PSA levels from year 2005 to 2015 were studied retrospectively. As a result of this research work, it can be concluded that a benign diagnosis can be given with a fair certainty when the PSA was below 4 ng/mL and a level of 100 ng/mL can be very unfavorable for the patients. This study helped to solidify the cancer screening protocols in Cayman Islands.

Conclusion

The PSA level can reassure and educate the patients towards the diagnosis of cancer of prostate in Cayman Islands. Benign diagnosis can be given with a fair certainty when the PSA was below 4 ng/mL and a level of 100 ng/mL can be very unfavorable for the patients. This study helped to solidify the cancer screening protocols in Cayman.

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Oral Administration of Clinical Stage Drug Candidate SENS-401 Effectively Reduces Cisplatin-induced Hearing Loss in Rats

Hypothesis: SENS-401, an oral clinical-stage drug, may reduce cisplatin-induced hearing loss and cochlear damage in an in vivo model. Background: Cisplatin is commonly associated with hearing loss, causing significant learning and behavioral difficulties in the pediatric cancer population, and for which there are currently no clinical solutions. SENS-401 has previously been shown to improve acoustic trauma-induced hearing loss in vivo. Methods: The effect of SENS-401 (R-azasetron besylate) on cisplatin IC50 values was evaluated in a panel of cisplatin-sensitive cell lines (NIH:OVCAR-3, SK-N-AS, NCI-H460, FaDu). Auditory brainstem response and distortion product otoacoustic emission tests were performed in a rat model of cisplatin-induced hearing-loss (8 mg/kg, day 1) at baseline, and after 14 days of SENS-401 (6.6, 13.2, 26.4 mg/kg/d). Cochlear outer hair cells were counted after immunolabeling for myosin-VIIa. Results: Cisplatin cytotoxicity was not impacted by the addition of SENS-401 (up to 10 μM) in any of the cell types evaluated. In vivo, all SENS-401 doses significantly improved auditory brainstem response threshold shift (up to 30 dB) and distortion product otoacoustic emission amplitude loss (up to 19 dB) over placebo. Body weight and survival were not significantly different between rats receiving placebo and those receiving 26.4 mg/kg SENS-401. Significantly more surviving outer hair cells were present after SENS-401 treatment compared with placebo (p 

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Venous Diverticula Causing Pulsatile Tinnitus Treated With Coil Embolization and Stent Placement With Resolution of Symptoms: Report of Two Cases and Review of the Literature

Objective: To report two cases of pulsatile tinnitus caused by complex venous diverticula with successful treatment via coil embolization and stent placement followed by complete resolution of symptoms. We also review the literature pertaining to venous diverticula causing pulsatile tinnitus treated using endovascular techniques. Patients: Two women patients, aged 27 and 29 years, presented to our institution with 3-month histories of pulsatile tinnitus. In each case, non-invasive imaging and conventional digital subtraction angiography (DSA) confirmed the presence of a complex right transverse-sigmoid sinus junction diverticulum. Intervention: Both patients underwent stent-assisted coil embolization of the venous diverticula. Main Outcome and Results: Clinical and DSA follow-up at 6 and 12 months confirmed resolution of symptoms with obliteration of the venous diverticulum. We also performed a PubMed database search for the period January 1995 through June 2016 using the terms pulsatile tinnitus, venous aneurysm/diverticulum, stent-assisted coil embolization, and endovascular treatment and identified reports of 14 additional patients treated using endovascular techniques. Conclusions: Venous sinus diverticula causing pulsatile tinnitus can be successfully treated with stent-assisted coil embolization with complete resolution of clinical symptoms. This is in concordance with 13 case reports in the literature involving 14 patients with venous sinus diverticula treated using endovascular techniques.

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Long-Term Patient-Reported Outcomes After Surgery for Superior Canal Dehiscence Syndrome

Objective: Evaluate the long-term patient-reported outcomes of surgery for superior canal dehiscence syndrome (SCDS). Study Design: Cross-sectional survey. Setting: Tertiary referral center. Patients: Adults who have undergone surgery for SCDS with at least 1 year since surgery. Main Outcome Measure(s): Primary outcome: change in symptoms that led to surgery. Secondary outcomes: change in 11 SCDS-associated symptoms, change in psychosocial metrics, and willingness to recommend surgery to friends with SCDS. Results: Ninety-three (43%) respondents completed the survey with mean (SD) time since surgery of 5.3 (3.6) years. Ninety-five percent of respondents reported the symptoms that led them to have surgery were "somewhat better," "much better," or "completely cured." Those with unilateral symptoms were more likely to report improvement than those with bilateral symptoms. There was no difference between those with short (1–5 yr) versus long (5–20 yr) follow-up. Each of the SCDS-associated symptoms showed significant improvement. The largest improvements were for autophony, pulsatile tinnitus, audible bodily sounds, and sensitivity to loud sound. Headaches, imbalance, dizziness, and brain fog showed the least improvements. Most patients reported improvements in quality of life, mood, and ability to function at work and socially. Ninety-five percent of patients would recommend SCDS surgery. Conclusions: Respondents demonstrated durable improvements in the symptoms that led them to have surgery. Auditory symptoms had the greatest improvements. Headaches, imbalance, dizziness, and brain fog showed the least improvements. Nearly, all patients would recommend SCDS surgery to others. These results can be used to counsel patients regarding the lasting benefits of surgery for SCDS.

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The Effect of Citalopram Versus a Placebo on Central Auditory Processing in the Elderly

Objective: Evaluate the effects of therapy with citalopram on the central auditory processing in the elderly measured by central auditory tests. Study Design: Prospective, randomized, double-blind, placebo-controlled study. Setting: Tertiary referral center. Patients: Thirty-nine patients older than 60 years with normal hearing thresholds or symmetrical sensorineural hearing loss up to 70 dBHL, word-recognition score equal to or better than 70%, and diagnosed with central auditory processing disorders completed the study. They underwent the mini-mental state examination, as a way to screen those with the possibility of dementia; they also underwent the Beck depression inventory, for screening individuals with depression. Intervention: Citalopram 20 mg/d or placebo for 6 months. Main Outcome Measure: The central auditory tests were applied to the selection of individuals with auditory processing disorders and repeated after 6 months' treatment. The tests were sound localization, speech in noise, dichotic digits test, pitch pattern sequence, duration pattern test, and gaps-in-noise. Results: Comparisons of central auditory tests pre- and posttreatment in groups showed: sound localization (p = 0.022), pitch pattern sequence humming (p = 0.110), pitch pattern sequence nomination (p = 0.355), duration pattern test humming (p = 0.801), duration pattern test nomination (p = 0.614), and gaps-in-noise (p = 0.230). Dichotic tests in right and left ears respectively: speech in noise (p = 0.949; p = 0.722), dichotic digits test (p = 0.943; p = 0.513). Conclusion: There was no clinical effect with the use of citalopram in central auditory processing tests of the subjects.

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Passive Transcutaneous Bone Conduction Hearing Implants: A Systematic Review

Objective: To systematically review the literature on currently available passive transcutaneous bone conduction hearing implants (pTCBI) with regard to complications, audiological outcomes, and quality-of-life scores. Data Sources: MEDLINE, EMBASE, Scopus, and Cochrane Library. Study Selection: All identified English-language articles reporting on the implantation of currently available pTCBI's and their complications. Both pediatric and adult patients were included. No limitation was placed on study design or level of evidence. Data Extraction: Complications, audiological outcomes including mean pure-tone average gain and mean speech reception threshold gain, and quality-of-life outcomes. Data Synthesis: Twenty-six articles were included in the review. Four hundred eighty-two pTCBIs have been reported in the literature. Major complications including skin breakdown, wound dehiscence, hematoma, seroma, and inability to use the device occurred in 5.2% of patients. Minor complications including pain and self-resolving erythema at the implant site occurred in 13.1% of the patients. The weighted mean pure-tone average gain of the two included devices was 28.4 ± 2.1 dB and the mean speech reception threshold gain was 32.9 ± 3.9 dB. Favorable quality-of-life scores have been demonstrated with pTCBIs. Conclusion: pTCBIs are a viable alternative to percutaneous devices in a carefully selected group of patients. These devices have demonstrated good audiological outcomes, low morbidity, and high patient satisfaction.

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Hearing Outcome With the Use of Glass Ionomer Cement as an Alternative to Crimping in Stapedotomy

Objective: To evaluate early hearing outcomes using glass ionomer cement to fix the Teflon piston prosthesis onto the long process of incus to minimize residual conductive hearing loss after stapedotomy. Study Design: Original report of prospective randomized control study. Setting: Tertiary referral center. Patients: A total of 80 consecutive patients with otosclerosis were randomized into two groups. Group A is a control group in which 40 patients underwent small fenestra stapedotomy using the classic technique. Group B included 40 patients who were subjected to small fenestra stapedotomy with fixation of the incus-prosthesis junction with glass ionomer bone cement. Interventions: Stapedotomy with the classical technique in group A and the alternative technique in group B. Primary Outcome Measure: The audiometric results before and after surgery. Results: Analysis of the results was performed using the paired t test to compare between pre and postoperative results. χ2 test was used to compare the results of the two groups. A p value less than 0.05 was considered significant from the statistical standpoint. Significant postoperative improvement of both pure-tone air conduction thresholds and air-bone gaps were reported in the two studied groups. The postoperative average residual air-bone gap and hearing gain were statistically significant in group B (p 

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Comparing Outcomes Following Salvage Microsurgery in Vestibular Schwannoma Patients Failing Gamma-knife Radiosurgery or Microsurgery

Objective: The increasing use of primary gamma-knife radiosurgery (GKS) for the treatment of vestibular schwannoma (VS) has led to a concomitant increase in the number of patients requiring salvage surgery for GKS failure. When patients underwent GKS as the primary treatment, it is known that dissecting tumor from adjacent nerves during salvage surgery is more difficult. In this report, we share our clinical experience with such patients and analyze the clinical findings of patients with tumor regrowth/recurrence. Study Design: Retrospective chart review. Setting: Tertiary center. Patients: Nine patients who underwent salvage surgery for VS regrowth/recurrence after GKS or microsurgery were enrolled. Main Outcome Measures: Symptom progression, radiological changes, intraoperative findings, and surgical outcomes were evaluated and compared. Results: Six patients with previous GKS and three with previous microsurgery underwent salvage microsurgery. The most obvious symptom of tumor regrowth was aggravation of hearing loss. Salvage surgery in all patients was limited to subtotal or near-total resection via a translabyrinthine/transotic approach. Severe adhesion, thickening, and fibrosis were more prominent findings in the GKS than in the previous microsurgery group. Dissection of the tumor from the facial nerve was more difficult in the GKS than in the microsurgery patients. Despite anatomical preservation of the facial nerve in all the six patients, three in the GKS group, but none in the revision microsurgery group, had worsening of facial nerve function. Conclusion: Salvage microsurgery of VS after failed GKS is more difficult than revision microsurgery, and the facial nerve outcomes are relatively poor. Therefore, the primary method of VS treatment should be carefully chosen. Additional imaging studies are recommended in patients with a sudden change in hearing loss who underwent GKS.

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Evaluation of Maximal Speech Intelligibility With Vibrant Soundbridge in Patients With Sensorineural Hearing Loss

Objective: The study investigated improvements in maximal speech intelligibility after Vibrant Soundbridge (VSB) implantation and analyzed the effect of the hearing loss pattern on maximal speech intelligibility represented by a phonetically balanced word score (PBmax). The effect of middle ear implants on PBmax has not been evaluated yet. Study Design: Study. Setting: Tertiary academic medical center. Patients/Interventions: Sixty patients who underwent VSB from December 2011 to January 2016 were retrospectively reviewed. All the patients had hearing aids preoperatively. Main Outcome Measures: Pure-tone and speech audiometry were checked with and without hearing aids and then with the VSB. The patients were divided into two groups: flat and down-sloping type of hearing loss. PBmax score was evaluated at the most comfortable listening level before and after VSB implantation and compared with scores with/without HA. Results: PBmax for both conventional HA and VSB were significantly higher compared with the unaided condition. The improvement in speech recognition was significantly better using VSB than using HA (p = 0.003). However, there was no significant difference in the improvement provided by VSB and HA in patients with a flat hearing loss. Patients with a down-sloping audiogram showed significantly better improvement with VSB than with HA (p = 0.003). Moreover, patients with greater preoperative high-frequency hearing loss had greater improvement in PBmax after VSB implantation. Conclusion: Speech intelligibility can be significantly improved by VSB implantation, especially in patients with a down-sloping hearing loss. This finding can help select patients who will benefit most from VSB implantation.

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Sensitivity and Specificity of Clinical and Laboratory Otolith Function Tests

Objective: To evaluate clinic based and laboratory tests of otolith function for their sensitivity and specificity in demarcating unilateral compensated complete vestibular deficit from normal. Study Design: Prospective cross-sectional study. Setting: Tertiary care hospital vestibular physiology laboratory. Subjects: Control group—30 healthy adults, 20–45 years age; Case group-15 subjects post vestibular shwannoma excision or post-labyrinthectomy with compensated unilateral complete audio-vestibular loss. Intervention: Otolith function evaluation by precise clinical testing (head tilt test—HTT; subjective visual vertical—SVV) and laboratory testing (headroll-eye counterroll—HR-ECR; vesibular evoked myogenic potentials—cVEMP). Main Outcome Measure: Sensitivity and specificity of clinical and laboratory tests in differentiating case and control subjects. Results: Measurable test results were universally obtained with clinical otolith tests (SVV; HTT) but not with laboratory tests. The HR-ECR test did not indicate any definitive wave forms in 10% controls and 26% cases. cVEMP responses were absent in 10% controls. HTT test with normative cutoff at 2 degrees deviations from vertical noted as 93.33% sensitive and 100% specific. SVV test with normative cutoff at 1.3 degrees noted as 100% sensitive and 100% specific. Laboratory tests demonstrated poorer specificities owing primarily to significant unresponsiveness in normal controls. Conclusions: Clinical otolith function tests, if conducted with precision, demonstrate greater ability than laboratory testing in discriminating normal controls from cases with unilateral complete compensated vestibular dysfunction.

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Patient-Reported Outcomes From the United States Clinical Trial for a Hybrid Cochlear Implant

Objective: To assess patient-reported outcomes (PROs) in individuals with significant residual low-frequency hearing and severe-to-profound high-frequency sensorineural hearing loss (SNHL) who received the hybrid cochlear implant (CI). Study Design: Prospective, multicenter, nonrandomized, single-arm repeated measures, single-subject design. Setting: Tertiary centers, ambulatory care. Patients: Fifty adults with severe-to-profound high-frequency SNHL and residual low-frequency hearing with aided word recognition scores between 10 and 60% in the ear to be implanted, and in the contralateral ear greater than or equal to implant ear less than or equal to 80%. Intervention: Therapeutic; hybrid CI. Main Outcome Measures: Speech, spatial and qualities of hearing scale (SSQ), device use questionnaire (DUQ), University of Washington Clinical Assessment of Music Perception (UW-CAMP) assessed preoperatively and after 6 and 12 (SSQ and DUQ only) months of hybrid CI use. Results: Significant improvements in mean SSQ ratings were demonstrated at 6 and 12 months postactivation overall and for domains related to speech hearing, spatial hearing, and sound quality. Significant improvement was also found for overall satisfaction on the DUQ and across a number of specific listening situations in addition to aspects related to social engagement. UW-CAMP pitch discrimination and melody and timbre recognition abilities were not compromised postoperatively, allowing hybrid subjects to maintain superior music perception abilities than typically observed with standard CIs. Conclusions: Patients who received the hybrid CI demonstrated significant PRO benefits on the SSQ and the DUQ after 6 and 12 months of CI use. In addition, given the opportunity to maintain useful low-frequency acoustic hearing, patients retained music listening abilities, as assessed by the UW-CAMP.

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Comparison of an Electromagnetic Middle Ear Implant and Hearing Aid Word Recognition Performance to Word Recognition Performance Obtained Under Earphones

Objective: To report the results of patients with the Maxum middle ear implant (MEI) and compare word recognition scores (WRS) and speech perception gap (SP Gap) of Maxum versus optimally fit hearing aids (HA). Study Design: Case series with chart review. Setting: Single, private otology clinic. Patients: Eleven ears, in nine adult patients (two women; average age 62.7 yr). Interventions: Twelve consecutive ears with moderate to severe sensorineural hearing loss (SNHL) underwent implantation of the Maxum system. One patient was not included due to inadequate preoperative testing. Main Outcome Measures: Primary outcome measures included word recognition score (WRS) and SP Gap (maximum word understanding [PB max] – WRSaided) improvement compared with HAs. Results: The average Maxum WRS was 64.7% (range, 28–94%), a 41.6% improvement (range, 10–66%) over HAs (p 

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Hearing Preservation During Cochlear Implantation and Electroacoustic Stimulation in Patients With SLC26A4 Mutations

Background and Objectives: Patients with SCL26A4 mutations presenting with Mondini deformity and enlarged vestibular aqueduct (EVA) tend to have comparable residual hearing. Although cochlear implantation (CI) produces good results in this group, deterioration of residual hearing can be an adverse event after surgery due to accompanying cochlear malformation and perilymph leakage during cochleostomy. The purpose of this study was to investigate if CI in patients with SCL26A4 mutations via the round window (RW) approach could achieve preservation of residual hearing, and to evaluate their speech reception with electroacoustic stimulation (EAS). Subjects and Methods: This is a retrospective chart review of eight patients with bilateral EVA, who were bi-allelic patients with SCL26A4 mutations. CI was performed in all patients by a single surgeon using the RW approach. Audiological results were compared before and after implantation. Results: Additional hearing loss after CI was less than 10 dBHL in five out of eight patients. Average hearing deterioration after CI was 8.75 dB (range, 0–26). Six out of eight patients used EAS mode after CI. The acoustic stimulation frequency ranged from 271 to 438 Hz. Patients showed better speech recognition in quiet and in noise using EAS mode compared with electrical stimulation alone. Conclusions: Preservation of residual hearing could be achieved after CI in patients with the SLC26A4 mutation via the RW approach. For successful preservation of residual hearing, application of newly-developed soft electrode and meticulous surgical is necessary. Our study showed that patients with the SLC26A4 mutation can be good candidates for EAS surgery.

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Clinical Characteristics of Benign Recurrent Vestibulopathy: Clearly Distinctive From Vestibular Migraine and Menière's Disease?

Objective: We aimed to systematically investigate the clinical characteristics of benign recurrent vestibulopathy (BRV), vestibular migraine (VM), and Menière's disease (MD) and to assess whether clinical symptoms exist that are unique to BRV. Study Design: Prospective cohort study. Setting: Tertiary referral center. Methods: Between January 2015 and November 2016, patients were prospectively recruited at a specialized dizziness clinic. Patients were included if they met the diagnostic criteria for BRV, VM, or MD which was evaluated by simultaneous consultation of an otorhinolaryngologist and neurologist. All patients received a comprehensive clinical examination that included vestibular tests and pure-tone audiometry. A questionnaire was designed to systematically document symptoms of the three vestibular disorders. Results: A total of 122 patients were included in our study, 65 (53%) were females in whom 29 (24%) were postmenopausal. The mean age was 55.5 ± 13.7 years and the mean age of onset of vertigo attacks was 49.2 ± 14.8 years (n = 119). Forty-five (37%) patients had a clinical diagnosis of BRV, 34 (28%) of VM, and 43 (35%) of MD. No symptom could be identified which was specifically linked to BRV. In patients with BRV, similar to those with VM, we found a female preponderance (p = 0.05 in BRV, p = 0.001 in VM). Patients with VM reported significantly more often a positive history of motion sickness (p = 0.01). In addition, canal paresis was most profound in patients with MD (p = 0.001). Conclusion: We found no clinical characteristics that were distinctive for BRV. However, we did find several distinctive clinical features for VM and MD which may assist the physician in their history taking.

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The Modified Rambo Transcanal Approach for Cochlear Implantation in CHARGE Syndrome

Objective: CHARGE syndrome is associated with a variety of temporal bone anomalies and deafness. The lack of surgical landmarks and facial nerve irregularities make cochlear implantation in this population a challenging endeavor. This study aims to describe a safe and efficacious transcanal approach for cochlear implantation that obviates the need to perform a mastoidectomy and facial recess. Patients: Three children with profound hearing loss secondary to CHARGE syndrome. Intervention: Transcanal cochlear implantation with closure of the ear canal via a modified Rambo meatoplasty. Main Outcome Measure(s): Retrospective chart review of temporal bone anomalies associated with CHARGE syndrome, technical nuances of this transcanal approach, and cochlear implant outcomes. Results: The mean patient age was 2.5 years (range 1.5–3.8 yr). Two were male and two were left ears. All patients had a hypoplastic mastoid, semicircular canal aplasia, and had some degree of cochlear dysplasia. A full cochlear implant insertion was achieved in all cases, even in the presence of grossly abnormal middle ear and facial nerve anatomy. There were no intraoperative or postoperative complications. The mean follow-up was 12.4 months (range, 3.9–25.2 mo). All three patients use their device daily. Their guardians report improved vocalization and environmental awareness. Conclusions: The modified Rambo transcanal approach provides a safe corridor for cochlear implantation in patients with CHARGE syndrome. This approach minimizes the anatomical variations associated with the syndrome and may reduce the risk of electrode extrusion. Implant outcomes in this patient population remain highly variable based on the patient's global cognitive capacity.

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The First Reported Case of Primary Intestinal-type Adenocarcinoma of the Middle Ear and Review of the Literature

Objective: Adenocarcinoma of the middle ear is a rare entity that must be distinguished from other adenomatous tumors of the temporal bone. We present the first patient of an intestinal-type adenocarcinoma originating from the middle ear. Patients: A 58-year-old woman presented with an 8-year history of left otorrhea. Her middle ear effusions were quite thick and gummy. She underwent eight sets of pressure-equalization tubes within 3 years. In 2011, her physical examination identified a middle ear mass, and she underwent mastoidectomy. A middle ear adenoma was resected. She underwent an additional three mastoidectomies for recurrence, with pathology from the 4th mastoidectomy revealing a diagnosis of adenocarcinoma. Imaging, at that time, showed an extensive temporal bone and Eustachian tube tumor. Interventions: She underwent a left subtotal temporal bone resection, parotidectomy, infratemporal fossa resection, dural resection, and microvascular free flap reconstruction followed by postoperative proton beam radiotherapy. Main Outcome Measures: The final pathology report revealed intestinal-type adenocarcinoma. Results: Treatment was successful and the patient remains disease free 4 years later. Conclusion: This is the first report of an intestinal-type adenocarcinoma of the middle ear and temporal bone. This patient also illustrates the difficulty of accurate histologic diagnosis of adenomatous tumors of the middle ear.

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Duration of Eligibility Prior to Cochlear Implantation: Have We Made Any Progress?

Objective: The objective is to determine if eligibility (as defined as the duration of severe to profound hearing loss before cochlear implantation [CI]) has changed over the 30 years since Food and Drug Administration approval. Data Sources: English-language, peer-reviewed articles, theses, and trial data available through PubMed and Cochrane Library databases up until and including May 31, 2016. Study Selection: One thousand six unique articles were identified. Prospective studies that reported duration of severe/profound hearing loss before CI in adult patients were included. Retrospective studies, reviews, meta-analyses, articles reporting pediatric or mixed data, hybrid/electroacoustic CI, and articles from centers outside the United States were excluded. Seventy-one studies met inclusion criteria and were included for analysis. Data Extraction: Contributing authors independently reviewed included studies for data validity and applicability. Data Synthesis: Metaregression was used to assess the relationship between the year of publication and duration of hearing loss. To account for a possible age effect, a second model was estimated including mean age at the time of study as a covariate. Conclusion: A positive association between study year and the duration of hearing loss before implantation was found showing a 0.28-year increase in the duration of hearing loss for every increasing study year. Contrary to conventional assumption, duration of eligibility for CI appears to be increasing. Though the reasons for this are not clear, current strategies to increase both awareness and access to CI seem to be falling short.

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Patulous Eustachian Tube Dysfunction: Patient Demographics and Comorbidities

Objective: The objective is to describe a large cohort of patients presenting with patulous Eustachian tube (pET) dysfunction. Study Design: Retrospective patient series. Setting: Tertiary referral center. Patients: All outpatient visits (2004–2016) that were assigned ICD9 code (381.7-Patulous Eustachian tube) were screened. Only patients with observed tympanic membrane movements during ipsilateral nasal breathing or acoustic reflex decay testing demonstrating transmitted nasal breathing were included (n = 190, n = 239 ears). Main Outcome Measures: Demographics and nasopharyngoscopy/otomicroscopy findings by comorbidities. Results: The majority (54%) was female and mean age of symptom onset was 38.0 (SD 20.0) years. Common symptoms included voice autophony (93%), breath autophony (92%), aural fullness (57%), pulsatile tinnitus (17%), and crackling or rumbling sounds (14%). Symptoms increased in frequency and duration with time (65%), were exacerbated with exercise (27%), and improved with placing the head in a dependent position (65%), sniffing (28%), upper respiratory infection (8%), and ipsilateral internal jugular vein compression (12%). In 52% pET was bilateral. Common comorbidities include environmental allergy (49%), weight loss (35%), laryngopharyngeal reflux (33%), anxiety (31%), autoimmunity (13%), and neuromuscular disease (8%). Allergy and anxiety patients were younger and more likely to have tonic contraction of the tensor veli palatini on exam (p 

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Using Electrically-evoked Compound Action Potentials to Estimate Perceptive Levels in Experienced Adult Cochlear Implant Users

Hypothesis: The cochlear implant (CI) fitting level prediction accuracy of electrically-evoked compound action potential (ECAP) should be enhanced by the addition of demographic data in models. Introduction: No accurate automated fitting of CI based on ECAP has yet been proposed. Methods: We recorded ECAP in 45 adults who had been using MED-EL CIs for more than 11 months and collected the most comfortable loudness level (MCL) used for CI fitting (prog-MCL), perception thresholds (meas-THR), and MCL (meas-MCL) measured with the stimulation used for ECAP recording. Linear mixed models taking into account cochlear site factors were computed to explain prog-MCL, meas-MCL, and meas-THR. Results: Cochlear region and ECAP threshold were predictors of the three levels. In addition, significant predictors were the ECAP amplitude for the prog-MCL and the duration of deafness for the prog-MCL and the meas-THR. Estimations were more accurate for the meas-THR, then the meas-MCL, and finally the prog-MCL. Conclusion: These results show that 1) ECAP thresholds are more closely related to perception threshold than to comfort level, 2) predictions are more accurate when the inter-subject and cochlear regions variations are considered, and 3) differences between the stimulations used for ECAP recording and for CI fitting make it difficult to accurately predict the prog-MCL from the ECAP recording. Predicted prog-MCL could be used as bases for fitting but should be used with care to avoid any uncomfortable or painful stimulation.

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RE: Skin Necrosis After Implantation with the Baha Attract: A Case Report and Review of the Literature: Chen SY, Mancuso D, and Lalwani AK. OTOL NEUROTOL 2017 MAR;38(3): 364–367

No abstract available

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The Relationship Between Environmental Sound Awareness and Speech Recognition Skills in Experienced Cochlear Implant Users

Hypothesis: 1) Environmental sound awareness (ESA) and speech recognition skills in experienced, adult cochlear implant (CI) users will be highly correlated, and, 2) ESA skills of CI users will be significantly lower than those of age-matched adults with normal hearing. Background: Enhancement of ESA is often discussed with patients with sensorineural hearing loss as a potential benefit of implantation and, in some cases, ESA may be a major motivating factor. Despite its ecological validity and patients' expectations, ESA remains largely a presumed skill. The relationship between ESA and speech recognition is not well-understood. Methods: ESA was assessed in 35 postlingually deaf, experienced CI users and a control group of 41 age-matched, normal hearing listeners using the validated, computerized familiar environmental sounds test—identification (FEST-I) and a diverse speech recognition battery. Demographic and audiological factors as well as nonverbal intelligence quotient (IQ)/nonverbal reasoning and spectral resolution were assessed. Results: Six of the 35 experienced CI users (17%) demonstrated FEST-I accuracy within the range of the NH controls. Among CI users all correlations between FEST-I accuracy and speech recognition scores were strong. Chronological age at the time of testing, duration of deafness, spectral resolution, and nonverbal IQ/nonverbal reasoning were strongly correlated with FEST-I accuracy. Partial correlation analysis showed that correlations between FEST-I and speech recognition measures remained significant when controlling for the demographic and audiological factors. Conclusion: Our findings reinforce the hypothesis that ESA and speech perception share common underlying processes rather than reflecting truly separate auditory domains.

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Reconnecting with Joseph and Augusta Dejerine: 100 hundred years on

Bajada et al. mark the centenary of Joseph Dejerine's death by demonstrating the continuing relevance of his research with his long-standing collaborator, Augusta Dejerine-Klumpke, on the white matter pathways of the brain to modern-day connectional anatomy. A first English translation of the original work is provided in the Supplementary Materials.

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The Assessment of the Danube River Water Pollution in Serbia

Abstract

Actual problems of water ecosystem pollution require the ecological classification and the identification of the most influential parameters on the variability of water quality, stressing the importance of both in the realization of the sustainable water management principles according to the Water Framework Directive European Union (WFD EU), and the preservation of the quality of the environment. The aim of this paper was the assessment of the ecological status of water quality and calculating water pollution index (WPI) of the Danube River in Serbia. For all surface waters, the WFD requires "good ecological status," i.e., low level changes of the natural state that occur as a result of human activities by 2015. The assessment was based on the data obtained from ten hydrological measuring stations on the Danube River in Serbia for 2014. It was ascertained that the ecological status of the Danube River water quality was class III, corresponding to "moderate ecological status" and deviating from the required "good ecological status." According to the calculated WPI = 1.352, the water pollution of the Danube River in Serbia was characterized as moderately polluted and corresponded to class III of surface water. The ecosystem approach clearly indicated that the concentration of physico-chemical parameters of the watercourse deviated from the target values. Therefore, there is an urgent need to take some measures to prevent pollution and improve the water quality of the Danube River as an integral part of the environment in Serbia.

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18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography May Exclude Malignancy in Sonographically Suspicious and Scintigraphically Hypofunctional Thyroid Nodules and Reduce Unnecessary Thyroid Surgeries

Thyroid , Vol. 0, No. 0.


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Long-Term Antithyroid Drug Treatment: A Systematic Review and Meta-Analysis

Thyroid , Vol. 0, No. 0.


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Comparison of Core-Needle Biopsy and Fine-Needle Aspiration for Evaluating Thyroid Incidentalomas Detected by 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography: A Propensity Score Analysis

Thyroid , Vol. 0, No. 0.


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Radioactive seed migration following parotid gland interstitial brachytherapy

Publication date: Available online 15 September 2017
Source:Brachytherapy
Author(s): Yi Fan, Ming-wei Huang, Yi-jiao Zhao, Hong Gao, Jian-Guo Zhang
PurposeTo evaluate the incidence and associated factors of pulmonary seed migration after parotid brachytherapy using a novel migrated seed detection technique.Methods and MaterialsPatients diagnosed with parotid cancer who underwent permanent parotid brachytherapy from January 2006 to December 2011 were reviewed retrospectively. Head and neck CT scans and chest X-rays were evaluated during routine follow-up. Mimics software and Geomagic Studio software were used for seed reconstruction and migrated seed detection from the original implanted region, respectively. Postimplant dosimetry analysis was performed after seeds migration if the seeds were still in their emitting count. Adverse clinical sequelae from seed embolization to the lung were documented.ResultsThe radioactive seed implants were identified on chest X-rays in 6 patients. The incidence rate of seed migration in 321 parotid brachytherapy patients was 1.87% (6/321) and that of individual seed migration was 0.04% (6/15218 seeds). All migrated seeds were originally from the retromandibular region. No adverse dosimetric consequences were found in the target region. Pulmonary symptoms were not reported by any patient in this study.ConclusionsIn our patient set, migration of radioactive seeds with an initial radioactivity of 0.6–0.7 mCi to the chest following parotid brachytherapy was rare. Late migration of a single seed from the central target region did not affect the dosimetry significantly, and patients did not have severe short-term complications. This study proposed a novel technique to localize the anatomical origin of the migrated seeds during brachytherapy. Our evidence suggested that placement of seeds adjacent to blood vessels was associated with an increased likelihood of seed migration to the lungs.



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Dangling regimes after free flap reconstruction of the lower limb; further evidence is required

We read with interest the recent systematic review by McGhee et al.1 on flap survival and morbidity following early post-operative rehabilitation after lower limb free flap reconstruction, where it was concluded that post-operative dangling confers physiological benefit in flap healing.

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Hot off the Press: Embedded Clinical Decision Support in Electronic Health Record Decreases Use of High-cost Imaging in the Emergency Department: EmbED study

Abstract

This longitudinal before/after study of embedded CDRs assessed the effects of clinical decision support on use of common imaging studies. Among high users, rates of CT-brain and CT c-spine were reduced after implementation of embedded clinical decision instruments, while in low users, rates increased. This article summarizes the manuscript and the Skeptics Guide to Emergency Medicine podcast, as well as the ensuing social media/online discussion.

This article is protected by copyright. All rights reserved.

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Challenges of developing small molecule kinase inhibitors for brain tumors and the need for emphasis on free drug levels.

Abstract

Despite biological rationale and significant clinical study, the pursuit of small molecule kinase inhibitors for the treatment of brain cancers has had very limited success. This Advance-in-Brief discusses the need for drugs to achieve free brain penetration to engage their targets where CNS tumors reside. This need to achieve free, as opposed to total, drug concentrations in the brain may be a contributing factor to why so many small molecule kinase inhibitors have not realized success in the neuro-oncology setting. For kinase targets of interest for brain cancer, the vast majority of small molecule inhibitors have either data suggesting free brain penetration would be limited or there is inadequate data to suggest that free brain penetration could be expected. Therefore, kinase targets of interest in the treatment of brain cancers may be inadequately assessed due to a lack of freely brain penetrant inhibitors available for clinical study. Encouraging recent drug discovery efforts that focused on achieving free brain penetration for cancers in the CNS are highlighted. Still, further efforts are needed to enable thorough clinical evaluation of biological hypotheses.

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PIK3CB/p110β is a Selective Survival Factor for Glioblastoma

Abstract

Background

Glioblastoma (GBM) is difficult to treat. Phosphoinositide 3-kinase (PI3K) is an attractive therapeutic target for GBM; however, targeting this pathway to effectively treat GBM is not successful because the roles of PI3K isoforms remain to be defined. The aim of this study is to determine whether PIK3CB/p110β, but not other PI3K isoforms, is a biomarker for GBM recurrence and important for cell survival.

Methods

Gene expression and clinical relevance of PI3K genes in GBM patients were analyzed using online databases. Expression/activity of PI3K isoforms was determined using immunoblotting. PI3K genes were inhibited using short-hairpin RNAs or isoform-selective inhibitors. Cell viability/growth was assessed by the MTS assay and Trypan blue exclusion assay. Apoptosis was monitored using the caspase activity assay. Mouse GBM xenograft models were used to gauge drug efficacy.

Results

PIK3CB/p110β was the only PI3K catalytic isoform that significantly correlated with high incidence rate, risk, and poor survival of recurrent GBM. PIK3CA/p110α, PIK3CB/p110β, and PIK3CD/p110δ were differentially expressed in GBM cell lines and primary tumor cells derived from patient specimens, whereas PIK3CG/p110γ was barely detected. PIK3CB/p110β protein levels presented a stronger association with the activities of PI3K signaling than other PI3K isoforms. Blocking p110β deactivated PI3K signaling, whereas inhibition of other PI3K isoforms had no effect. Specific inhibitors of PIK3CB/p110β, but not other PI3K isoforms, remarkably suppressed viability and growth of GBM cells and xenograft tumors in mice, with minimal cytotoxic effects on astrocytes.

Conclusions

PIK3CB/p110β is a biomarker for GBM recurrence and selectively important for GBM cell survival.

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Trivalent CAR T-cells Overcome Interpatient Antigenic Variability in Glioblastoma

Abstract

Background

Glioblastoma (GBM) is the most common primary malignant brain cancer, and is currently incurable. Chimeric Antigen Receptor (CAR) T-cells have shown promise in GBM treatment. While we have shown that combinatorial targeting of two glioma antigens offsets antigen escape and enhances T-cell effector functions, the inter-patient variability in surface antigen expression between patients hinders the clinical impact of targeting two antigen pairs. This study addresses targeting 3 antigens using a single CAR T-cell product for broader application.

Methods

We analyzed the surface expression of 3 targetable glioma antigens (HER2, IL13Rα2 and EphA2) in 15 primary GBM samples. Accordingly, we created a trivalent T-cell product armed with three CAR molecules specific for these validated targets encoded by a single universal (U) tricistronic transgene (UCAR T-cells).

Results

Our data showed that co-targeting HER2, IL13Rα2 and EphA2 could overcome inter-patient variability by a tendency to capture near 100% of tumor cells in most tumors tested in this cohort. UCAR T-cells made from GBM patients' blood uniformly expressed all three CAR molecules with distinct antigen specificity. UCAR T-cells mediated robust immune synapses with tumor targets forming more polarized microtubule organizing centers (MTOC) and exhibited improved cytotoxicity and cytokine release over best monospecific and bispecific CAR T-cells per patient tumor profile. Lastly, low doses of UCAR T-cells controlled established autologous GBM patient derived xenografts (PDX) and improved survival of treated animals.

Conclusions

UCAR T-cells can overcome antigenic heterogeneity in GBM and lead to improved treatment outcomes.

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Early assessment of response to induction therapy in acute myeloid leukemia using 18 F-FLT PET/CT

Abstract

Background

We evaluated the suitability of ¹⁸F-fluorodeoxythymidine (¹⁸F-FLT) positron emission tomography (PET)/computed tomography (CT) for assessment of the early response to induction therapy and its value for predicting clinical outcome in patients with acute myeloid leukemia (AML). Adult patients who had histologically confirmed AML and received induction therapy were enrolled. All patients underwent ¹⁸F-FLT PET/CT after completion of induction. PET/CT images were visually and quantitatively assessed. Cases with intensely increased bone marrow uptake in more than one third of the long bones and throughout the central skeleton were interpreted as PET-positive for resistant disease (RD). PET results were compared to the clinical response and outcome.

Results

In visual PET analysis of 10 eligible patients (7 male, 3 female; median age 58 years), 5 patients were interpreted as being PET-positive and 5 as PET-negative. Standardized uptake values were significantly different between PET-positive and PET-negative groups. Eight of 10 patients achieved clinical complete remission (CR)/CR with incomplete blood count recovery (CRi). Five CR/CRi patients had PET-negative findings, but 3 CR patients had PET-positive findings. Both of the RD patients had PET-positive findings. During follow-up, 2 CR patients with PET-positive findings relapsed, or were strongly suspected of relapse, 4 months after consolidation.

Conclusion

¹⁸F-FLT PET/CT after induction therapy showed good sensitivity and negative-predictive value for evaluating RD in patients with AML. This preliminary study suggests that ¹⁸F-FLT PET/CT may be valuable as a noninvasive tool for early assessment of the response to treatment and may provide prognostic value for survival in patients with AML.

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An undergraduate Otolaryngology curriculum comparison in the United Kingdom using a curriculum evaluation framework

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Bile acids: a potential role in the pathogenesis of pharyngeal malignancy

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Assessment of carotid artery intima‐media thickness in patients with obstructive sleep apnoea

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Single‐sided deafness affects language and auditory development – a case–control study

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Local extension staging of sinonasal tumours: retrospective comparison between CT/MRI assessment and pathological findings

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Adaptation and validation of the Singing Voice Handicap Index into Polish

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An evaluation of the quality of evidence available to inform current bone conducting hearing device national policy

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Effect on mortality of elective parathyroid surgery in one hundred and three patients with chronic kidney disease: our experience

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The value of direct audiology access for magnetic resonance imaging: an audit of 40 cases

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Dura and sinus compression with a transcutaneous bone conduction device – hearing outcomes and safety in 38 patients

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Congenital anosmia: our experience of eleven patients with aplasia or hypoplasia of the olfactory tract

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UK tertiary centre experience of outcomes from osseointegrated transcutaneous magnetic bone conduction hearing system implanted in twenty‐five patients using a linear incision technique

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Short‐term results from seventy‐six patients receiving a bone‐anchored hearing implant installed with a novel minimally invasive surgery technique

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Squamous cell carcinoma associated with inverted papilloma of the maxillary sinus: our experience with 21 patients

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Functional magnetic resonance imaging in seven borderline cochlear implant candidates: a preliminary research study

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Balloon tuboplasty in patients with Eustachian tube dysfunction: a prospective study in 39 patients (55 ears)

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A retrospective analysis of seven patients with acquired immunodeficiency syndrome and pharyngeal and/or laryngeal Talaromyces marneffei infection

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Workload and costs of audiological assessment on tertiary settings: Data analysis and audit

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The role of sentinel lymph node biopsy in the management of laryngeal carcinoma

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Insulin effect on hearing recovery in idiopathic sudden sensorineural hearing loss: Retrospective study of 145 patients

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Complete biochemical response after pulmonary metastasectomy in prostate adenocarcinoma

Abstract

Background

Prostate cancer most commonly metastasizes to bones or lymph nodes, and metastatic prostate cancer is suggestive of disseminated disease. Metastatic disease is usually not amenable to surgery.

Case presentation

The current report presents a unique case of in which the excision of a solitary pulmonary metastasis resulted in undetectable prostate-specific antigen.

Conclusion

This case and others suggest metastasectomy could be considered in cases with solitary metastasis, and physicians should have a careful discussion regarding risks and possible benefits from surgical excision.

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Monoclonal antibodies directed against cadherin RGD exhibit therapeutic activity against melanoma and colorectal cancer metastasis

Purpose: New targets are required for the control of advanced metastatic disease. We investigated the use of cadherin RGD motifs, which activate the α2β1integrin pathway, as targets for the development of therapeutic monoclonal antibodies (mAbs). Experimental Design: CDH17 fragments and peptides were prepared and used for immunization and antibody development. Antibodies were tested for inhibition of β1 integrin and cell adhesion, proliferation and invasion assays using cell lines from different cancer types: colorectal, pancreatic, melanoma and breast cancer. Effects of the mAbs on cell signaling were determined by Western blot. Nude mice were used for survival analysis after treatment with RGD-specific mAbs and metastasis development. Results: Antibodies against full-length CDH17 failed to block the binding to α2β1 integrin. However, CDH17 RGD peptides generated highly selective RGD mAbs that blocked (CDH17 and VE-cadherin)-mediated β1 integrin activation in melanoma, breast, pancreatic and colorectal cancer cells. Antibodies provoked a significant reduction in cell adhesion and proliferation of metastatic cancer cells. Treatment with mAbs impaired the integrin signaling pathway activation of FAK in colorectal cancer, of JNK and ERK kinases, in colorectal and pancreatic cancers, and of JNK, ERK, Src and AKT in melanoma and breast cancers. In vivo, RGD-specific mAbs increased mouse survival after inoculation of melanoma and colorectal cancer cell lines to cause lung and liver metastasis, respectively. Conclusions: Blocking the interaction between RGD cadherins and α2β1 integrin with highly selective mAbs constitutes a promising therapy against advanced metastatic disease in colon cancer, melanoma and, potentially, other cancers.

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Demethylation therapy as a targeted treatment for human papilloma virus-associated head and neck cancer

Purpose:DNA methylation in human papillomavirus-associated (HPV+) head and neck squamous cell carcinoma (HNSCC) may have importance for continuous expression of HPV oncogenes, tumor cell proliferation and survival. Here, we determined activity of a global DNA demethylating agent, 5-azacytidine (5-aza), against HPV+ HNSCC in pre-clinical models and explored it as a targeted therapy in a window trial enrolling patients with HPV+ HNSCC. Experimental Design: Sensitivity of HNSCC cells to 5-aza treatment was determined, then 5-aza activity was tested in vivo using xenografted tumors in a mouse model. Finally, tumor samples from patients enrolled in a window clinical trial were analyzed to identify activity of 5-aza therapy in patients with HPV+ HNSCC. Results: Clinical trial and experimental data show that 5-aza induced growth inhibition and cell death in HPV+ HNSCC. 5-aza reduced expression of HPV genes, stabilized p53, and induced p53-dependent apoptosis in HNSCC cells and tumors. 5-aza repressed expression and activity of matrix metalloproteinases (MMPs) in HPV+ HNSCC, activated interferon response in some HPV+ head and neck cancer cells, and inhibited the ability of HPV+ xenografted tumors to invade mouse blood vessels. Conclusions: 5-aza may provide effective therapy for HPV-associated HNSCC as an alternative or complement to standard cytotoxic therapy.

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Dosimetric comparison of different treatment modalities for stereotactic radiotherapy

Abstract

Background

The modalities for performing stereotactic radiotherapy (SRT) on the brain include the cone-based linear accelerator (linac), the flattening filter-free (FFF) volumetric modulated arc therapy (VMAT) linac, and tomotherapy. In this study, the cone-based linac, FFF-VMAT linac, and tomotherapy modalities were evaluated by measuring the differences in doses delivered during brain SRT and experimentally assessing the accuracy of the output radiation doses through clinical measurements.

Methods

We employed a homemade acrylic dosimetry phantom representing the head, within which a thermoluminescent dosimeter (TLD) and radiochromic EBT3 film were installed. Using the conformity/gradient index (CGI) and Paddick methods, the quality of the doses delivered by the various SRT modalities was evaluated. The quality indicators included the uniformity, conformity, and gradient indices. TLDs and EBT3 films were used to experimentally assess the accuracy of the SRT dose output.

Results

The dose homogeneity indices of all the treatment modalities were lower than 1.25. The cone-based linac had the best conformity for all tumors, regardless of the tumor location and size, followed by the FFF-VMAT linac; tomography was the worst-performing treatment modality in this regard. The cone-based linac had the best gradient, regardless of the tumor location and size, whereas the FFF-VMAT linac had a better gradient than tomotherapy for a large tumor diameter (28 mm). The TLD and EBT3 measurements of the dose at the center of tumors indicated that the average difference between the measurements and the calculated dose was generally less than 4%. When the 3% 3-mm gamma passing rate metric was used, the average passing rates of all three treatment modalities exceeded 98%.

Conclusions

Regarding the dose, the cone-based linac had the best conformity and steepest dose gradient for tumors of different sizes and distances from the brainstem. The results of this study suggest that SRT should be performed using the cone-based linac on tumors that require treatment plans with a steep dose gradient, even as the tumor is slightly irregular, we should also consider using a high dose gradient of the cone base to treat and protect the normal tissue. If normal tissues require special protection exist at positions that are superior or inferior to the tumor, we can consider using tomotherapy or Cone base with couch at 0° for treatment.

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T cells deficient in diacylglycerol kinase-{zeta} are resistant to PD-1 inhibition and help create persistent host immunity to leukemia

Efforts to improve the efficacy of adoptive T cell therapies and immune checkpoint therapies in myelogenous leukemia are desired. In this study, we evaluated the anti-leukemia activity of adoptively transferred polyclonal cancer antigen-reactive T cells deficient in the regulator diacylglycerol kinase-zeta (DGKζ) with or without PD-1/PD-L1 blockade. In the C1498 mouse model of myeloid leukemia, we showed that leukemia was eradicated more effectively in DGKζ-deficient (DGKζ-/-) mice than wild-type mice. T cells transferred from DGKζ-deficient mice to wild-type tumor-bearing recipients conferred this benefit. Leukemia clearance was similar to mice treated with anti-PD-L1. Strikingly, we found that the activity of adoptively transferred DGKζ-/- T cells relied partly on induction of sustainable host T cell immunity. Transferring DGKζ-deficient T cells increased the levels of IFN-γ and other cytokines in recipient mice, especially with co-administration of anti-PD-L1. Overall, our results offered evidence that targeting DGKζ may leverage the efficacy of adoptive T cell and immune checkpoint therapies in leukemia treatment. Further, they suggest that DGKζ targeting might decrease risks of antigen escape or resistance to immune checkpoint blockade.

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Tenascin-C and integrin {alpha}9 mediate interactions of prostate cancer with the bone microenvironment

Deposition of the extracellular matrix protein tenascin-C is part of the reactive stroma response, which has a critical role in prostate cancer progression. Here we report that tenascin-C is expressed in the bone endosteum and involved associated with formation of prostate bone metastases. Metastatic cells cultured on osteo-mimetic surfaces coated with tenascin-C exhibited enhanced adhesion and colony formation as mediated by integrin α9β1. Additionally, metastatic cells preferentially migrated and colonized tenascin-C-coated trabecular bone xenografts in a novel system that employed chorioallantoic membranes of fertilized chicken eggs as host. Overall, our studies deepen knowledge about reactive stroma responses in the bone endosteum that accompany prostate cancer metastasis to trabecular bone, with potential implications to therapeutically target this process in patients.

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Tethering IL2 to its receptor IL2R{beta} enhances anti-tumor activity and expansion of natural killer NK92 cells

Interleukin-2 (IL2) is an immunostimulatory cytokine for key immune cells including T cells and natural killer (NK) cells. Systemic IL2 supplementation could enhance NK-mediated immunity in a variety of diseases ranging from neoplasms to viral infection. However, its systemic use is restricted by its serious side effects and limited efficacy due to activation of T regulatory cells (Tregs). IL2 signaling is mediated through interactions with a multi-subunit receptor complex containing IL2Rα, IL2Rβ and IL2Rγ. Adult natural killer (NK) cells express only IL2Rβ and IL2Rγ subunits and are therefore relatively insensitive to IL2. To overcome these limitations, we created a novel chimeric IL2-IL2Rβ fusion protein of IL2 and its receptor IL2Rβ joined via a peptide linker (CIRB). NK92 cells expressing CIRB (NK92CIRB) were highly activated and expanded indefinitely without exogenous IL2. When compared to an IL2-secreting NK92 cell line, NK92CIRB were more activated, cytotoxic and resistant to growth inhibition. Direct contact with cancer cells enhanced the cytotoxic character of NK92CIRB cells, which displayed superior in vivo antitumor effects in mice. Overall, our results showed how tethering IL2 to its receptor IL2Rβ eliminates the need for IL2Rα and IL2Rβ, offering a new tool to selectively activate and empower immune therapy.

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YAP suppresses lung squamous cell carcinoma progression via deregulation of the DNp63-GPX2 axis and ROS accumulation

Lung squamous cell carcinoma (SCC), accounting for approximately 30% of non-small cell lung cancer, is often refractory to therapy. Screening a small molecule library, we identified digitoxin as a high potency compound for suppressing human lung SCC growth in vitro and in vivo. Mechanistic investigations revealed that digitoxin attenuated YAP phosphorylation and promoted YAP nuclear sequestration. YAP activation led to excessive accumulation of reactive oxygen species (ROS) by downregulating the antioxidant enzyme GPX2 in a manner related to p63 blockade. In patient-derived xenograft (PDX) models, digitoxin treatment efficiently inhibited lung SCC progression in correlation with reduced expression of YAP. Collectively, our results highlight a novel tumor suppressor function of YAP via downregulation of GPX2 and ROS accumulation, with potential implications to improve precision medicine of human lung SCC.

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Chemotherapy-induced macrophage infiltration into tumors enhances nanographene-based photodynamic therapy

Increased recruitment of tumor-associated macrophages (TAM) to tumors following chemotherapy promotes tumor resistance and recurrence and correlates with poor prognosis. TAM depletion suppresses tumor growth, but is not highly effective due to the effects of tumorigenic mediators from other stromal sources. Here we report that adoptive macrophage transfer led to a dramatically enhanced photodynamic therapy (PDT) effect of 2-(1-hexyloxyethyl)-2-devinyl pyropheophor-bide-alpha (HPPH)-coated polyethylene glycosylated nanographene oxide [GO(HPPH)-PEG] by increasing its tumor accumulation. Moreover, tumor treatment with commonly used chemotherapeutic drugs induced an increase in macrophage infiltration into tumors, which also enhanced tumor uptake and the PDT effects of GO(HPPH)-PEG, resulting in tumor eradication. Macrophage recruitment to tumors after chemotherapy was visualized noninvasively by near-infrared fluorescence and single-photon emission computed tomography imaging using F4/80-specific imaging probes. Our results demonstrate that chemotherapy combined with GO(HPPH)-PEG PDT is a promising strategy for the treatment of tumors, especially those resistant to chemotherapy. Furthermore, TAM-targeted molecular imaging could potentially be used to predict the efficacy of combination therapy and select patients who would most benefit from this treatment approach.

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Biallelic Dicer1 loss mediated by aP2-Cre drives angiosarcoma

Angiosarcoma is an aggressive vascular sarcoma with an extremely poor prognosis. Due to the relative rarity of this disease, its molecular drivers and optimal treatment strategies are obscure. DICER1 is an RNase III endoribonuclease central to microRNA biogenesis, and germline DICER1 mutations result in a cancer predisposition syndrome, associated with an increased risk of many tumor types. Here we show that biallelic Dicer1 deletion with aP2-Cre drives aggressive and metastatic angiosarcoma independent of other genetically engineered oncogenes or tumor suppressor loss. Angiosarcomas in aP2-Cre;Dicer1Flox/- mice histologically and genetically resemble human angiosarcoma. MicroRNA-23 target genes including the oncogenes Ccnd1 as well as Adam19, Plau, and Wsb1 that promote invasiveness and metastasis were enriched in mouse and human angiosarcoma. These studies illustrate that Dicer1 can function as a traditional loss-of-function tumor suppressor gene, and they provide a fully penetrant animal model for the study of angiosarcoma development and metastasis.

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LSD1-Mediated Epigenetic Reprogramming Drives CENPE Expression and Prostate Cancer Progression

Androgen receptor (AR) signaling is a key driver of prostate cancer (PCa), and androgen-deprivation therapy (ADT) is a standard treatment for patients with advanced and metastatic disease. However, patients receiving ADT eventually develop incurable castration-resistant PCa (CRPC). Here we report that the chromatin modifier LSD1, an important regulator of AR transcriptional activity, undergoes epigenetic reprogramming in CRPC. LSD1 reprogramming in this setting activated a subset of cell cycle genes including CENPE, a centromere binding protein and mitotic kinesin. CENPE was regulated by the co-binding of LSD1 and AR to its promoter, which was associated with loss of RB1 in CRPC. Notably, genetic deletion or pharmacological inhibition of CENPE significantly decrease tumor growth. Our findings show how LSD1-mediated epigenetic reprogramming drives CRPC, and they offer a mechanistic rationale for its therapeutic targeting in this disease.

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HMGB proteins and arthritis

Abstract

The high-mobility group box (HMGB) family includes four members: HMGB1, 2, 3 and 4. HMGB proteins have two functions. In the nucleus, HMGB proteins bind to DNA in a DNA structure-dependent but nucleotide sequence-independent manner to function in chromatin remodeling. Extracellularly, HMGB proteins function as alarmins, which are endogenous molecules released upon tissue damage to activate the immune system. HMGB1 acts as a late mediator of inflammation and contributes to prolonged and sustained systemic inflammation in subjects with rheumatoid arthritis. By contrast, Hmgb2 ^−/− mice represent a relevant model of aging-related osteoarthritis (OA), which is associated with the suppression of HMGB2 expression in cartilage. Hmgb2 mutant mice not only develop early-onset OA but also exhibit a specific phenotype in the superficial zone (SZ) of articular cartilage. Given the similar expression and activation patterns of HMGB2 and β-catenin in articular cartilage, the loss of these pathways in the SZ of articular cartilage may lead to altered gene expression, cell death and OA-like pathogenesis. Moreover, HMGB2 regulates chondrocyte hypertrophy by mediating Runt-related transcription factor 2 expression and Wnt signaling. Therefore, one possible mechanism explaining the modulation of lymphoid enhancer binding factor 1 (LEF1)-dependent transactivation by HMGB2 is that a differential interaction between HMGB2 and nuclear factors affects the transcription of genes containing LEF1-responsive elements. The multiple functions of HMGB proteins reveal the complex roles of these proteins as innate and endogenous regulators of inflammation in joints and their cooperative roles in cartilage hypertrophy as well as in the maintenance of joint tissue homeostasis.

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Prévention du vieillissement, techniques chirurgicales récentes et voies d’avenir de la chirurgie du rajeunissement facial

Publication date: Available online 15 September 2017
Source:Annales de Chirurgie Plastique Esthétique
Author(s): C. Le Louarn
La prévention du vieillissement est avant tout liée à une bonne hygiène de vie, qui reste indépendante des causes génétiques d'accentuation du vieillissement. Les causes du vieillissement structurel du visage varient de la gravité à la perte de volume, à la contraction des muscles de la mimique, additionné du vieillissement biologique naturel des tissus concernés. Parmi les techniques chirurgicales récentes, on peut s'intéresser : pour la région frontale au lifting endoscopique et au lifting du front non endoscopique. Le lifting des sourcils par excision cutanée au-dessus du sourcil peut simplifier certaines situations ; pour la région centro-faciale, le risque reste la malposition palpébrale secondaire. Pour l'éviter on peut réaliser un Smas jugal sus-zygomatique associé à une réinjection de graisse ou faire un lifting temporo-malaire, plus efficaces en latéral qu'en médio-palpébral. Pour une action plus médiane avec une élévation verticale, soit existent des lifting centro-faciaux avec ouverture complète de l'orbiculaire palpébral, soit très limitée en externe comme dans le lifting malaire concentrique, pour minimiser cette malposition palpébrale. Une proposition de traitement du délicat chemosis par injection corticoïde malaire inféro-externe préperiostée est envisagée. Sur l'ovale, la section du depressor anguli oris et de la suspension de l'espace pré masséterin restent intéressantes. Enfin, sur le cou, en plus des actions sur le bord postérieur du platysma ou sur les digastriques, un lambeau de platysma latéral suspendu à la mastoïde est intéressant. Une dernière technique de lift du cou, avec fixation du platysma au fascia cervical profond et associée au lambeau platysmal latéral est proposée pour essayer de stabiliser le mieux possible cette région en limitant les risques.Prevention of aging is mainly obtained through appropriate health practices, modulated by the genetic causes of aging. Causes of facial structural aging include gravity, volume loss, contraction of the mimic muscles and obviously biological aging of tissues. Among the very numerous new surgical technique of facial rejuvenation, we could point out: for the frontal region, obviously we are focus on the endoscopic and non-endoscopic frontal lifts. But also, we should note the transcutaneous Brow Shaping which with a well defined, step by step technique is indeed a simple way to improve a possible difficult situation; concerning the mid-face lift, as the main risk is the secondary eyelid malposition, a high Smas or a temporo-malar lift can be performed. It ensures a good temporal effect but there is nearly no improvement at the mid-pupilla level. A mid-face lift is nevertheless mandatory to achieve an efficient skin removal on the mid-pupilla line. This is performed most of the time with a complete orbicularis oculi muscle opening, and only with a small lateral opening in case of the concentric malar lift, which minimize the risk of eyelid malposition. Based on a new description of the lymphatic draining of the lower lid, a new treatment of the chemosis is proposed with a corticoid injection at infero-lateral part of the malar area, in the preperiosteal plane. For the oval, the DAO section and the suspension of the middle premasseter space beyond the anterior border of the masseter where the Smas overlies the buccal fat pad, stay efficients. Regarding the neck, the suspension of the posterior border of the platysma to the Loré's fascia, the digastric corset with or without a platysma corset are advanced and valuable techniques. Lately, a new option was described using a lateral skin-platysma flap to minimize platysma bands and even more recently a neck lift with fixation of the anterior platysma to the deep cervical fascia and suspension of the lateral platysma flap.



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La jonction palpébro-jugale

Publication date: Available online 15 September 2017
Source:Annales de Chirurgie Plastique Esthétique
Author(s): C. Volpei, J. Fernandez, B. Chignon-Sicard
La région palpébro-jugale est une région clé qui inspire tous les commentaires : de l'air fatigué à la bonne mine, en passant par l'aspect reposé, sans oublier bien-sûr le charme, la beauté, la jeunesse. Malgré une palette de techniques médicales et chirurgicales intéressante, le traitement de cette région est parfois difficile et les résultats ne sont pas toujours à la hauteur de nos espérances. La blépharoplastie standardisée de soustraction utilisée de façon abusive pour des indications souvent bien différentes a montré ses limites. La lipostructure a révolutionné la blépharoplastie et est devenue avec ses derniers raffinements une technique de référence. Les liftings centro-faciaux sous-périostés apportent des résultats incomparables au prix d'une agressivité technique certaine. La médecine esthétique propose des solutions alternatives ou complémentaires dignes d'intérêt. Nous avons passé en revue les différentes procédures à notre disposition avec leurs atouts et leurs limites et nous avons tenté de codifier les indications thérapeutiques. Le positionnement du sillon palpébro-jugal clinique par rapport au rebord orbitaire inférieur influence notre stratégie quant au choix des techniques retenues.The eyelid-cheek junction is a key area which generates many comments: from looking tired to looking good or rested, without forgetting charm, beauty, and a youthful appearance. In spite of many interesting medical and surgical procedures, treating this area is sometimes difficult and results are not always up to our expectations. Standardized blepharoplasty, which has often been improperly used, has shown its limits. Since the latest refinements, lipostructure has revolutionised blepharoplasty and serving as a reference, it has become an established technique. Subperiostal mediofacial lift allows outstanding results at the cost of a certain technical aggressiveness. Aesthetic medicine proposes worthy alternative and/or appropriate complementary solutions. Different procedures we dispose of have been reviewed together with their assets and their limits. A codification of therapeutic indications is proposed. The positioning of the eyelid-cheek clinical junction in relation with the low orbital bone rim influences our strategy in choosing the appropriate technique.



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JAAA CEU Program.

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JAAA CEU Program.

J Am Acad Audiol. 2017 Sep;28(8):770-771

Authors:

PMID: 28906247 [PubMed - in process]

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The Relationship between Central Auditory Processing, Language, and Cognition in Children Being Evaluated for Central Auditory Processing Disorder.

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The Relationship between Central Auditory Processing, Language, and Cognition in Children Being Evaluated for Central Auditory Processing Disorder.

J Am Acad Audiol. 2017 Sep;28(8):758-769

Authors: Brenneman L, Cash E, Chermak GD, Guenette L, Masters G, Musiek FE, Brown M, Ceruti J, Fitzegerald K, Geissler K, Gonzalez J, Weihing J

Abstract
BACKGROUND: Pediatric central auditory processing disorder (CAPD) is frequently comorbid with other childhood disorders. However, few studies have examined the relationship between commonly used CAPD, language, and cognition tests within the same sample.
PURPOSE: The present study examined the relationship between diagnostic CAPD tests and "gold standard" measures of language and cognitive ability, the Clinical Evaluation of Language Fundamentals (CELF) and the Wechsler Intelligence Scale for Children (WISC).
RESEARCH DESIGN: A retrospective study.
STUDY SAMPLE: Twenty-seven patients referred for CAPD testing who scored average or better on the CELF and low average or better on the WISC were initially included. Seven children who scored below the CELF and/or WISC inclusion criteria were then added to the dataset for a second analysis, yielding a sample size of 34.
DATA COLLECTION AND ANALYSIS: Participants were administered a CAPD battery that included at least the following three CAPD tests: Frequency Patterns (FP), Dichotic Digits (DD), and Competing Sentences (CS). In addition, they were administered the CELF and WISC. Relationships between scores on CAPD, language (CELF), and cognition (WISC) tests were examined using correlation analysis.
RESULTS: DD and FP showed significant correlations with Full Scale Intelligence Quotient, and the DD left ear and the DD interaural difference measures both showed significant correlations with working memory. However, ∼80% or more of the variance in these CAPD tests was unexplained by language and cognition measures. Language and cognition measures were more strongly correlated with each other than were the CAPD tests with any CELF or WISC scale. Additional correlations with the CAPD tests were revealed when patients who scored in the mild-moderate deficit range on the CELF and/or in the borderline low intellectual functioning range on the WISC were included in the analysis.
CONCLUSIONS: While both the DD and FP tests showed significant correlations with one or more cognition measures, the majority of the variance in these CAPD measures went unexplained by cognition. Unlike DD and FP, the CS test was not correlated with cognition. Additionally, language measures were not significantly correlated with any of the CAPD tests. Our findings emphasize that the outcomes and interpretation of results vary as a function of the subject inclusion criteria that are applied for the CELF and WISC. Including participants with poorer cognition and/or language scores increased the number of significant correlations observed. For this reason, it is important that studies investigating the relationship between CAPD and other domains or disorders report the specific inclusion criteria used for all tests.

PMID: 28906246 [PubMed - in process]

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Potential Audiological and MRI Markers of Tinnitus.

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Potential Audiological and MRI Markers of Tinnitus.

J Am Acad Audiol. 2017 Sep;28(8):742-757

Authors: Gopal KV, Thomas BP, Nandy R, Mao D, Lu H

Abstract
BACKGROUND: Subjective tinnitus, or ringing sensation in the ear, is a common disorder with no accepted objective diagnostic markers.
PURPOSE: The purpose of this study was to identify possible objective markers of tinnitus by combining audiological and imaging-based techniques.
RESEARCH DESIGN: Case-control studies.
STUDY SAMPLE: Twenty adults drawn from our audiology clinic served as participants. The tinnitus group consisted of ten participants with chronic bilateral constant tinnitus, and the control group consisted of ten participants with no history of tinnitus. Each participant with tinnitus was closely matched with a control participant on the basis of age, gender, and hearing thresholds.
DATA COLLECTION AND ANALYSES: Data acquisition focused on systematic administration and evaluation of various audiological tests, including auditory-evoked potentials (AEP) and otoacoustic emissions, and magnetic resonance imaging (MRI) tests. A total of 14 objective test measures (predictors) obtained from audiological and MRI tests were subjected to statistical analyses to identify the best predictors of tinnitus group membership. The least absolute shrinkage and selection operator technique for feature extraction, supplemented by the leave-one-out cross-validation technique, were used to extract the best predictors. This approach provided a conservative model that was highly regularized with its error within 1 standard error of the minimum.
RESULTS: The model selected increased frontal cortex (FC) functional MRI activity to pure tones matching their respective tinnitus pitch, and augmented AEP wave N₁ amplitude growth in the tinnitus group as the top two predictors of tinnitus group membership. These findings suggest that the amplified responses to acoustic signals and hyperactivity in attention regions of the brain may be a result of overattention among individuals that experience chronic tinnitus.
CONCLUSIONS: These results suggest that increased functional MRI activity in the FC to sounds and augmented N₁ amplitude growth may potentially be the objective diagnostic indicators of tinnitus. However, due to the small sample size and lack of subgroups within the tinnitus population in this study, more research is needed before generalizing these findings.

PMID: 28906245 [PubMed - in process]

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Hearing Aid Use and Mild Hearing Impairment: Learnings from Big Data.

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Hearing Aid Use and Mild Hearing Impairment: Learnings from Big Data.

J Am Acad Audiol. 2017 Sep;28(8):731-741

Authors: Timmer BHB, Hickson L, Launer S

Abstract
BACKGROUND: Previous research, mostly reliant on self-reports, has indicated that hearing aid (HA) use is related to the degree of hearing impairment (HI). No large-scale investigation of the relationship between data-logged HA use and HI has been conducted to date.
PURPOSE: This study aimed to investigate if objective measures of overall daily HA use and HA use in various listening environments are different for adults with mild HI compared to adults with moderate HI.
RESEARCH DESIGN: This retrospective study used data extracted from a database of fitting appointments from an international group of HA providers. Only data from the participants' most recent fitting appointment were included in the final dataset.
STUDY SAMPLE: A total of 8,489 bilateral HA fittings of adults over the age of 18 yr, conducted between January 2013 and June 2014, were included. Participants were subsequently allocated to HI groups, based on British Society of Audiology and American Speech-Language-Hearing Association audiometric descriptors.
DATA COLLECTION AND ANALYSIS: Fitting data from participating HA providers were regularly transferred to a central server. The data, with all personal information except age and gender removed, contained participants' four-frequency average (at 500, 1000, 2000, and 4000 Hz) as well as information on HA characteristics and usage. Following data cleaning, bivariate and post hoc statistical analyses were conducted.
RESULTS: The total sample of adults' average daily HA use was 8.52 hr (interquartile range [IQR] = 5.49-11.77) in the left ear and 8.51 hr (IQR = 5.49-11.72) in the right ear. With a few exceptions, there were no statistical differences between hours of HA use for participants with mild HI compared to those with moderate impairment. Across all mild and moderate HI groups, the most common overall HA usage was between 8 and 12 hr per day. Other factors such as age, gender, and HA style also showed no relationship to hours of use. HAs were used, on average, for 7 hr (IQR = 4.27-9.96) per day in quiet and 1 hr (IQR = 0.33-1.41) per day in noisy listening situations.
CONCLUSIONS: Clinical populations with mild HI use HAs as frequently as those with a moderate HI. These findings support the recommendation of HAs for adults with milder degrees of HI.

PMID: 28906244 [PubMed - in process]

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Pediatric Hearing Aid Management: Challenges among Hispanic Families.

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Pediatric Hearing Aid Management: Challenges among Hispanic Families.

J Am Acad Audiol. 2017 Sep;28(8):718-730

Authors: Caballero A, Muñoz K, White K, Nelson L, Domenech-Rodriguez M, Twohig M

Abstract
BACKGROUND: Hearing aid fitting in infancy has become more common in the United States as a result of earlier identification of hearing loss. Consistency of hearing aid use is an area of concern for young children, as well as other hearing aid management challenges parents encounter that may contribute to less-than-optimal speech and language outcomes. Research that describes parent hearing aid management experiences of Spanish-speaking Hispanic families, or the extent of their needs, is not available. To effectively support parent learning, in a culturally sensitive manner, providers may benefit from having a better understanding of the needs and challenges Hispanic families experience with hearing aid management.
PURPOSE: The purpose of the current study was to describe challenges with hearing aid management and use for children from birth to 5 yr of age, as reported by Spanish-speaking parents in the United States, and factors that may influence hearing aid use.
RESEARCH DESIGN: This study used a cross-sectional survey design.
STUDY SAMPLE: Forty-two Spanish-speaking parents of children up to 5 yr of age who had been fitted with hearing aids.
DATA COLLECTION AND ANALYSIS: Responses were obtained from surveys mailed to parents through early intervention programs and audiology clinics. Descriptive statistics were used to describe frequencies and variance in responses.
RESULTS: Forty-seven percent of the parents reported the need for help from an interpreter during audiology appointments. Even though parents received information and were taught skills by their audiologist, many wanted to receive more information. For example, 59% wanted to know how to meet other parents of children who have hearing loss, although 88% had previously received this information; 56% wanted to know how to do basic hearing aid maintenance, although 71% had previously received instruction. The two most frequently reported hearing aid use challenges were fear of losing the hearing aids, and not seeing benefit from the hearing aids. Hearing aid use during all waking hours was reported by more parents (66%) when their child had a good day than when their child had a bad day (37%); during the previous two weeks, 35% of the parents indicated their child had all good days.
CONCLUSIONS: Hispanic parents wanted more comprehensive information, concrete resources, and emotional support from the audiologist to overcome hearing aid management challenges. Understanding parents' perspectives, experiences, and challenges is critical for audiologists to provide appropriate support in a culturally sensitive manner and to effectively address families' needs.

PMID: 28906243 [PubMed - in process]

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Safe Use of Acoustic Vestibular-Evoked Myogenic Potential Stimuli: Protocol and Patient-Specific Considerations.

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Safe Use of Acoustic Vestibular-Evoked Myogenic Potential Stimuli: Protocol and Patient-Specific Considerations.

J Am Acad Audiol. 2017 Sep;28(8):708-717

Authors: Portnuff CDF, Kleindienst S, Bogle JM

Abstract
BACKGROUND: Vestibular-evoked myogenic potentials (VEMPs) are commonly used clinical assessments for patients with complaints of dizziness. However, relatively high air-conducted stimuli are required to elicit the VEMP, and ultimately may compromise safe noise exposure limits. Recently, research has reported the potential for noise-induced hearing loss (NIHL) from VEMP stimulus exposure through studies of reduced otoacoustic emission levels after VEMP testing, as well as a recent case study showing permanent sensorineural hearing loss associated with VEMP exposure.
PURPOSE: The purpose of this report is to review the potential for hazardous noise exposure from VEMP stimuli and to suggest clinical parameters for safe VEMP testing.
RESEARCH DESIGN: Literature review with presentation of clinical guidelines and a clinical tool for estimating noise exposure.
RESULTS: The literature surrounding VEMP stimulus-induced hearing loss is reviewed, including several cases of overexposure. The article then presents a clinical calculation tool for the estimation of a patient's safe noise exposure from VEMP stimuli, considering stimulus parameters, and includes a discussion of how varying stimulus parameters affect a patient's noise exposure. Finally, recommendations are provided for recognizing and managing specific patient populations who may be at higher risk for NIHL from VEMP stimulus exposure. A sample protocol is provided that allows for safe noise exposure.
CONCLUSIONS: VEMP stimuli have the potential to cause NIHL due to high sound exposure levels. However, with proper safety protocols in place, clinicians may reduce or eliminate this risk to their patients. Use of the tools provided, including the noise exposure calculation tool and sample protocols, may help clinicians to understand and ensure safe use of VEMP stimuli.

PMID: 28906242 [PubMed - in process]

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Tracking of Noise Tolerance to Measure Hearing Aid Benefit.

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Tracking of Noise Tolerance to Measure Hearing Aid Benefit.

J Am Acad Audiol. 2017 Sep;28(8):698-707

Authors: Kuk F, Seper E, Lau CC, Korhonen P

Abstract
BACKGROUND: The benefits offered by noise reduction (NR) features on a hearing aid had been studied traditionally using test conditions that set the hearing aids into a stable state of performance. While adequate, this approach does not allow the differentiation of two NR algorithms that differ in their timing characteristics (i.e., activation and stabilization time).
PURPOSE: The current study investigated a new method of measuring noise tolerance (Tracking of Noise Tolerance [TNT]) as a means to differentiate hearing aid technologies. The study determined the within-session and between-session reliability of the procedure. The benefits provided by various hearing aid conditions (aided, two NR algorithms, and a directional microphone algorithm) were measured using this procedure. Performance on normal-hearing listeners was also measured for referencing.
RESEARCH DESIGN: A single-blinded, repeated-measures design was used.
STUDY SAMPLE: Thirteen experienced hearing aid wearers with a bilaterally symmetrical (≤10 dB) mild-to-moderate sensorineural hearing loss participated in the study. In addition, seven normal-hearing listeners were tested in the unaided condition.
DATA COLLECTION AND ANALYSIS: Participants tracked the noise level that met the criterion of tolerable noise level (TNL) in the presence of an 85 dB SPL continuous discourse passage. The test conditions included an unaided condition and an aided condition with combinations of NR and microphone modes within the UNIQUE hearing aid (omnidirectional microphone, no NR; omnidirectional microphone, NR; directional microphone, no NR; and directional microphone, NR) and the DREAM hearing aid (omnidirectional microphone, no NR; omnidirectional microphone, NR). Each tracking trial lasted 2 min for each hearing aid condition. Normal-hearing listeners tracked in the unaided condition only. Nine of the 13 hearing-impaired listeners returned after 3 mo for retesting in the unaided and aided conditions with the UNIQUE hearing aid. The individual TNL was estimated for each participant for all test conditions. The TNT index was calculated as the difference between 85 dB SPL and the TNL.
RESULTS: The TNT index varied from 2.2 dB in the omnidirectional microphone, no NR condition to -4.4 dB in the directional microphone, NR on condition. Normal-hearing listeners reported a TNT index of -5.7 dB using this procedure. The averaged improvement in TNT offered by the NR algorithm on the UNIQUE varied from 2.1 dB when used with a directional microphone to 3.0 dB when used with the omnidirectional microphone. The time course of the NR algorithm was different between the UNIQUE and the DREAM hearing aids, with the UNIQUE reaching a stable TNL sooner than the DREAM. The averaged improvement in TNT index from the UNIQUE directional microphone was 3.6 dB when NR was activated and 4.4 dB when NR was deactivated. Together, directional microphone and NR resulted in a total TNT improvement of 6.5 dB. The test-retest reliability of the procedure was high, with an intrasession 95% confidence interval (CI) of 2.2 dB and an intersession 95% CI of 4.2 dB.
CONCLUSIONS: The effect of the NR and directional microphone algorithms was measured to be 2-3 and 3.6-4.4 dB, respectively, using the TNT procedure. Because of its tracking property and reliability, this procedure may hold promise in differentiating among some hearing aid features that also differ in their time course of action.

PMID: 28906241 [PubMed - in process]

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Listening Effort Measured in Adults with Normal Hearing and Cochlear Implants.

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Listening Effort Measured in Adults with Normal Hearing and Cochlear Implants.

J Am Acad Audiol. 2017 Sep;28(8):685-697

Authors: Perreau AE, Wu YH, Tatge B, Irwin D, Corts D

Abstract
BACKGROUND: Studies have examined listening effort in individuals with hearing loss to determine the extent of the impairment. Regarding cochlear implants (CIs), results suggest that listening effort is improved using bilateral CIs compared to unilateral CIs. Few studies have investigated listening effort and outcomes related to the hybrid CI.
PURPOSE: Here, we compared listening effort across three CI groups, and to a normal-hearing control group. The impact of listener traits, that is, age, age at onset of hearing loss, duration of CI use, and working memory capacity, were examined relative to listening effort.
RESEARCH DESIGN: The participants completed a dual-task paradigm with a primary task identifying sentences in noise and a secondary task measuring reaction time on a Stroop test. Performance was assessed for all participant groups at different signal-to-noise ratios (SNRs), ranging in 2-dB steps from 0 to +10 dB relative to an individual's SNR-50, at which the speech recognition performance is 50% correct. Participants completed three questions on listening effort, the Spatial Hearing Questionnaire, and a reading span test.
STUDY SAMPLE: All 46 participants were adults. The four participant groups included (1) 12 individuals with normal hearing, (2) 10 with unilateral CIs, (3) 12 with bilateral CIs, and (4) 12 with a hybrid short-electrode CI and bilateral residual hearing.
DATA COLLECTION AND ANALYSIS: Results from the dual-task experiment were compared using a mixed 4 (hearing group) by 6 (SNR condition) analysis of variance (ANOVA). Questionnaire results were compared using one-way ANOVAs, and correlations between listener traits and the objective and subjective measures were compared using Pearson correlation coefficients.
RESULTS: Significant differences were found in speech perception among the normal-hearing and the unilateral and the bilateral CI groups. There was no difference in primary task performance among the hybrid CI and the normal-hearing groups. Across the six SNR conditions, listening effort improved to a greater degree for the normal-hearing group compared to the CI groups. However, there was no significant difference in listening effort between the CI groups. The subjective measures revealed significant differences between the normal-hearing and CI groups, but no difference among the three CI groups. Across all groups, age was significantly correlated with listening effort. We found no relationship between listening effort and the age at the onset of hearing loss, age at implantation, the duration of CI use, and working memory capacity for these participants.
CONCLUSIONS: Listening effort was reduced to a greater degree for the normal-hearing group compared to the CI users. There was no significant difference in listening effort among the CI groups. For the CI users in this study, age was a significant factor with regard to listening effort, whereas other variables such as the duration of CI use and the age at the onset of hearing loss were not significantly related to listening effort.

PMID: 28906240 [PubMed - in process]

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Auditory Processing Testing: In the Booth versus Outside the Booth.

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Auditory Processing Testing: In the Booth versus Outside the Booth.

J Am Acad Audiol. 2017 Sep;28(8):679-684

Authors: Lucker JR

Abstract
BACKGROUND: Many audiologists believe that auditory processing testing must be carried out in a soundproof booth. This expectation is especially a problem in places such as elementary schools. Research comparing pure-tone thresholds obtained in sound booths compared to quiet test environments outside of these booths does not support that belief. Auditory processing testing is generally carried out at above threshold levels, and therefore may be even less likely to require a soundproof booth. The present study was carried out to compare test results in soundproof booths versus quiet rooms.
PURPOSE: The purpose of this study was to determine whether auditory processing tests can be administered in a quiet test room rather than in the soundproof test suite. The outcomes would identify that audiologists can provide auditory processing testing for children under various test conditions including quiet rooms at their school.
RESEARCH DESIGN: A battery of auditory processing tests was administered at a test level equivalent to 50 dB HL through headphones. The same equipment was used for testing in both locations.
STUDY SAMPLE: Twenty participants identified with normal hearing were included in this study, ten having no auditory processing concerns and ten exhibiting auditory processing problems. All participants underwent a battery of tests, both inside the test booth and outside the booth in a quiet room. Order of testing (inside versus outside) was counterbalanced.
DATA COLLECTION AND ANALYSIS: Participants were first determined to have normal hearing thresholds for tones and speech. Auditory processing tests were recorded and presented from an HP EliteBook laptop computer with noise-canceling headphones attached to a y-cord that not only presented the test stimuli to the participants but also allowed monitor headphones to be worn by the evaluator. The same equipment was used inside as well as outside the booth.
RESULTS: No differences were found for each auditory processing measure as a function of the test setting or the order in which testing was done, that is, in the booth or in the room.
CONCLUSIONS: Results from the present study indicate that one can obtain the same results on auditory processing tests, regardless of whether testing is completed in a soundproof booth or in a quiet test environment. Therefore, audiologists should not be required to test for auditory processing in a soundproof booth. This study shows that audiologists can conduct testing in a quiet room so long as the background noise is sufficiently controlled.

PMID: 28906239 [PubMed - in process]

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