Faculty Bibliography

INTRODUCTION/UNASSIGNED:Chronic pain negatively impacts a range of sensory and affective behaviors. Previous studies have shown that the presence of chronic pain not only causes hypersensitivity at the site of injury but may also be associated with pain-aversive experiences at anatomically unrelated sites. While animal studies have indicated that the cingulate and prefrontal cortices are involved in this generalized hyperalgesia, the mechanisms distinguishing increased sensitivity at the site of injury from a generalized site-nonspecific enhancement in the aversive response to nociceptive inputs are not well known. METHODS/UNASSIGNED: = 15) by analyzing behavioral and electroencephalographic (EEG) data. RESULTS/UNASSIGNED:As expected, participants with chronic pain endorsed enhanced pain with mechanical stimuli in both back and hand. We further analyzed electroencephalographic (EEG) recordings during these evoked pain episodes. Brain oscillations in theta and alpha bands in the medial orbitofrontal cortex (mOFC) were associated with localized hypersensitivity, while increased gamma oscillations in the anterior cingulate cortex (ACC) and increased theta oscillations in the dorsolateral prefrontal cortex (dlPFC) were associated with generalized hyperalgesia. DISCUSSION/UNASSIGNED:These findings indicate that chronic pain may disrupt multiple cortical circuits to impact nociceptive processing.

OBJECTIVE:The purpose of this study was to determine the extent to which sensory integration strategies via head sway, derived from a Head-Mounted Display (HMD), change in people with vestibular disorders following vestibular rehabilitation. DESIGN/METHODS:Randomized Controlled TrialSetting:Vestibular Rehabilitation ClinicParticipants:Thirty participants with vestibular dysfunction and 21 age-matched controls. MAIN OUTCOME MEASURES/METHODS:Participants experienced two levels of visual surround (static or moving 'stars', front to back at 0.2 Hz, 32 mm) and white noise (none or rhythmic) while their head sway was recorded via the HTC Vive. We quantified head sway via Directional Path (DP) and Root Mean Square Velocity (RMSV) in 5 directions: anterior-posterior, medio-lateral, pitch, yaw, and roll and Power Spectral Density in low (PSD 1), medium (PSD 2) and high (PSD 3) frequencies in the anterior-posterior direction. INTERVENTIONS/METHODS:Participants performed the assessment prior to being randomized into 8-weeks of contextual sensory integration training in virtual reality or traditional vestibular rehabilitation and once again following completion of the intervention. Controls performed the assessment once. Twelve participants dropped out, half due to covid lock-down. We applied an intention to treat analysis. RESULTS:We observed significant increases in AP DP, RMSV and all PSDs with change in visual level. Both intervention groups significantly decreased medio-lateral, pitch and roll DP and RMSV and anterior-posterior PSD 2 with no group differences. Vestibular participants were significantly higher than controls on all outcomes pre rehabilitation. Post rehabilitation they were only significantly higher on PSD 2. Sound was not a significant predictor of head sway in this protocol. CONCLUSIONS:Head sway decreased following vestibular rehabilitation regardless of visual load or type of intervention applied. This change was measured via head kinematics derived from a portable HMD which can serve as a sensitive in-clinic assessment for tracking improvement over time.

INTRODUCTION/UNASSIGNED:Cochlear implants (CIs) provide access to sound for children and adults who do not receive adequate benefit from hearing aids. Age at implantation is known to affect outcomes across the lifespan. AREAS COVERED/UNASSIGNED:The effects of age on CI outcomes are examined for infants, children, adolescents, and older adults. A variety of outcome measures are considered, including speech perception, language, cognition, and quality of life measures. EXPERT OPINION/COMMENTARY/UNASSIGNED:For those meeting candidacy criteria, CIs are beneficial at any age. In general, younger age is related to greater benefit when considering pre-lingual deafness. Other factors such as additional disabilities, may mitigate this effect. Post-lingually deafened adults demonstrate similar benefit regardless of age, though the oldest individuals (80+) may see smaller degrees of improvement from preoperative scores. Benefit can be measured in many ways, and the areas of greatest benefit may vary based on age: young children appear to see the greatest effects of age at implantation on language measures, whereas scores on cognitive measures appear to be most impacted for the oldest population. Future research should consider implantation at extreme ages (5-9 months or > 90 years), unconventional measures of CI benefit including qualitative assessments, and longitudinal designs.

INTRODUCTION/UNASSIGNED:In spite of its apparent ease, comprehension of spoken discourse represents a complex linguistic and cognitive operation. The difficulty of such an operation can increase when the speech is degraded, as is the case with cochlear implant users. However, the additional challenges imposed by degraded speech may be mitigated to some extent by the linguistic context and pace of presentation. METHODS/UNASSIGNED:An experiment is reported in which young adults with age-normal hearing recalled discourse passages heard with clear speech or with noise-band vocoding used to simulate the sound of speech produced by a cochlear implant. Passages were varied in inter-word predictability and presented either without interruption or in a self-pacing format that allowed the listener to control the rate at which the information was delivered. RESULTS/UNASSIGNED:Results showed that discourse heard with clear speech was better recalled than discourse heard with vocoded speech, discourse with a higher average inter-word predictability was better recalled than discourse with a lower average inter-word predictability, and self-paced passages were recalled better than those heard without interruption. Of special interest was the semantic hierarchy effect: the tendency for listeners to show better recall for main ideas than mid-level information or detail from a passage as an index of listeners' ability to understand the meaning of a passage. The data revealed a significant effect of inter-word predictability, in that passages with lower predictability had an attenuated semantic hierarchy effect relative to higher-predictability passages. DISCUSSION/UNASSIGNED:Results are discussed in terms of broadening cochlear implant outcome measures beyond current clinical measures that focus on single-word and sentence repetition.

Human leukocyte antigen (HLA) molecular mismatch is a powerful biomarker of rejection. Few studies have explored its use in assessing rejection risk in heart transplant recipients. We tested the hypothesis that a combination of HLA Epitope Mismatch Algorithm (HLA-EMMA) and Predicted Indirectly Recognizable HLA Epitopes (PIRCHE-II) algorithms can improve risk stratification of pediatric heart transplant recipients. Class I and II HLA genotyping were performed by next-generation sequencing on 274 recipient/donor pairs enrolled in the Clinical Trials in Organ Transplantation in Children (CTOTC). Using high-resolution genotypes, we performed HLA molecular mismatch analysis with HLA-EMMA and PIRCHE-II, and correlated these findings with clinical outcomes. Patients without pre-formed donor specific antibody (DSA) (n=100) were used for correlations with post-transplant DSA and antibody mediated rejection (ABMR). Risk cut-offs were determined for DSA and ABMR using both algorithms. HLA-EMMA cut-offs alone predict the risk of DSA and ABMR; however, if used in combination with PIRCHE-II, the population could be further stratified into low-, intermediate-, and high-risk groups. The combination of HLA-EMMA and PIRCHE-II enables more granular immunological risk stratification. Intermediate-risk cases, like low-risk cases, are at a lower risk of DSA and ABMR. This new way of risk evaluation may facilitate individualized immunosuppression and surveillance.

OBJECTIVE:To describe the natural history of primary inner ear schwannomas over a long follow-up period. STUDY DESIGN/METHODS:Retrospective case series. SETTING/METHODS:Tertiary referral center. PATIENTS/METHODS:Patients with primary inner ear schwannomas with serial audiometric and radiologic follow-up. MAIN OUTCOME MEASURES/METHODS:Patterns of hearing loss, rate of hearing decline, presence of vestibular symptoms, and rate of tumor growth. RESULTS:A total of 12 patients with 13 tumors were identified. The mean duration of follow-up was 7 years. Forty-six percent of tumors were intracochlear, 15% were intravestibular, 23% were transmodiolar, and 15% were intravestibular-cochlear. Hearing loss was the most common presenting symptom, occurring in all patients. Among patients with serviceable hearing (AAO Class A or B) at the time of presentation, the average time to decline to a nonserviceable hearing level was 57.3 months (range, 21-117 mo). Hearing loss was sudden in 31% of patients, progressive in 61% and fluctuating in 8%. No patients had intractable vertigo; however, two required vestibular physiotherapy. On initial magnetic resonance imaging, the mean largest tumor dimension was 3.1 mm (standard deviation, 1.2 mm), and the mean largest dimension on most recent magnetic resonance imaging was 4.4 mm (standard deviation, 1.1 mm). Two tumors exhibited no growth over a follow-up of 11.3 and 2.8 years, respectively. Overall, the mean growth was 0.25 mm per year followed. Two patients underwent cochlear implantation with simultaneous tumor resection and had favorable outcomes. CONCLUSION/CONCLUSIONS:Long-term follow-up suggests a conservative approach, with possible hearing rehabilitation at the time of deterioration, is a safe management strategy for primary inner ear schwannomas.

OBJECTIVE:To prospectively evaluate the frailty phenotype in a population of older adults and determine its association with 1) perioperative complications, 2) need for vestibular rehabilitation after surgery, and 3) early speech perception outcomes. STUDY DESIGN/METHODS:Prospective cohort study. SETTING/METHODS:Tertiary care hospital. PATIENTS/METHODS:Adults older than 65 years undergoing cochlear implantation. INTERVENTIONS/METHODS:The Fried Frailty Index was used to classify patients as frail, prefrail, or not frail based on five criteria: 1) gait speed, 2) grip strength, 3) unintentional weight loss, 4) weekly physical activity, and 5) self-reported exhaustion. MAIN OUTCOMES MEASURES/METHODS:Rates of intraoperative and postoperative complications, postoperative falls, need for vestibular rehabilitation, and early speech perception outcomes. RESULTS:Forty-six patients were enrolled in this study. Five patients (10.8%) were categorized as frail and 10 (21.7%) as prefrail. The mean ages of frail, prefrail, and not frail patients were 80.9, 78.8, and 77.5, respectively. There were no intraoperative complications among all groups. Three patients required postoperative vestibular rehabilitation; all were not frail. One postoperative fall occurred in a nonfrail individual. Mean (standard deviation) device use times at 3 months in frail, prefrail, and not frail patients were 7.6 (3.5), 11.1 (3.6), and 11.6 (2.9) hours per day, respectively. Consonant-nucleus-consonant word scores 3 months after surgery in frail, prefrail, and not frail patients were 13% (12.2), 44% (19.7), and 51% (22.4), respectively. The median (range) number of missed follow-up visits (surgeon, audiologist, speech language pathologist combined) was 7 (1-10) in frail patients, compared with a median of 3 (0-4) and 2 (0-5) in prefrail and not frail patients. CONCLUSIONS:Frail patients did not have increased rates of surgical complications, need for vestibular rehabilitation, or postoperative falls. However, frail patients experienced challenges in accessing postoperative care, which may be addressed by using remote programming and rehabilitation.