Faculty Bibliography

BACKGROUND/UNASSIGNED:Central nervous system (CNS) cancer is the 10th leading cause of cancer-associated deaths for adults, but the leading cause in pediatric patients and young adults. The variety and complexity of histologic subtypes can lead to diagnostic errors. DNA methylation is an epigenetic modification that provides a tumor type-specific signature that can be used for diagnosis. METHODS/UNASSIGNED:We performed a prospective study using DNA methylation analysis as a primary diagnostic method for 1921 brain tumors. All tumors received a pathology diagnosis and profiling by whole genome DNA methylation, followed by next-generation DNA and RNA sequencing. Results were stratified by concordance between DNA methylation and histopathology, establishing diagnostic utility. RESULTS/UNASSIGNED:Of the 1602 cases with a World Health Organization histologic diagnosis, DNA methylation identified a diagnostic mismatch in 225 cases (14%), 78 cases (5%) did not classify with any class, and in an additional 110 (7%) cases DNA methylation confirmed the diagnosis and provided prognostic information. Of 319 cases carrying 195 different descriptive histologic diagnoses, DNA methylation provided a definitive diagnosis in 273 (86%) cases, separated them into 55 methylation classes, and changed the grading in 58 (18%) cases. CONCLUSIONS/UNASSIGNED:DNA methylation analysis is a robust method to diagnose primary CNS tumors, improving diagnostic accuracy, decreasing diagnostic errors and inconclusive diagnoses, and providing prognostic subclassification. This study provides a framework for inclusion of DNA methylation profiling as a primary molecular diagnostic test into professional guidelines for CNS tumors. The benefits include increased diagnostic accuracy, improved patient management, and refinements in clinical trial design.

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.

BACKGROUND/UNASSIGNED:The 2016 WHO classification described a subtype of midline gliomas harboring histone 3 (H3) K27M alterations, and the 2021 edition added a new subtype of hemispheric diffuse gliomas with H3 G34R/V mutations. The incidence and clinical behavior of leptomeningeal disease (LMD) in these patients is not well defined. METHODS/UNASSIGNED:Retrospective study of patients with H3-altered gliomas diagnosed from 01/2012 to 08/2021; histone mutations were identified through next-generation sequencing (NGS) of tumor biopsy and/or cerebrospinal fluid (CSF). RESULTS/UNASSIGNED:< .0001). CONCLUSIONS/UNASSIGNED:In our cohort, 50% of patients developed LMD. Although further studies are needed, CSF ctDNA characterization may aid in identifying molecular tumor profiles in glioma patients with LMD, and neuroaxis imaging and CSF NGS should be considered for early LMD detection.

Speech that has been artificially accelerated through time compression produces a notable deficit in recall of the speech content. This is especially so for adults with cochlear implants (CI). At the perceptual level, this deficit may be due to the sharply degraded CI signal, combined with the reduced richness of compressed speech. At the cognitive level, the rapidity of time-compressed speech can deprive the listener of the ordinarily available processing time present when speech is delivered at a normal speech rate. Two experiments are reported. Experiment 1 was conducted with 27 normal-hearing young adults as a proof-of-concept demonstration that restoring lost processing time by inserting silent pauses at linguistically salient points within a time-compressed narrative ("time-restoration") returns recall accuracy to a level approximating that for a normal speech rate. Noise vocoder conditions with 10 and 6 channels reduced the effectiveness of time-restoration. Pupil dilation indicated that additional effort was expended by participants while attempting to process the time-compressed narratives, with the effortful demand on resources reduced with time restoration. In Experiment 2, 15 adult CI users tested with the same (unvocoded) materials showed a similar pattern of behavioral and pupillary responses, but with the notable exception that meaningful recovery of recall accuracy with time-restoration was limited to a subgroup of CI users identified by better working memory spans, and better word and sentence recognition scores. Results are discussed in terms of sensory-cognitive interactions in data-limited and resource-limited processes among adult users of cochlear implants.

OBJECTIVE/UNASSIGNED:Tracheostomy tube change is a multistep skill that must be performed rapidly and precisely. Despite the critical importance of this skill, there is wide variation in teaching protocols. METHODS/UNASSIGNED:An innovative operant conditioning teaching methodology was employed and compared to traditional educational techniques. Medical student volunteers at a tertiary care academic institution (Albert Einstein College of Medicine) were recruited and randomly distributed into 2 groups: operant vs traditional (control). Following the educational session, each group was provided with practice time and then asked to perform 10 tracheostomy tube changes. Performance was recorded and scored by blinded raters using deidentified video recordings. RESULTS/UNASSIGNED: = 0.427). DISCUSSION/UNASSIGNED:Although the operant conditioning methodology necessarily requires a greater time to teach, the results support this methodology over traditional learning modalities as it enhances accuracy in the acquired skill. Operant learning methodology is under consideration for other skills and education sessions in our program. Future steps include the application and adaptation of this education model to students and residents in other settings and fields. IMPLICATIONS FOR PRACTICE/UNASSIGNED:Operant learning is effective for teaching multistep skills such as tracheostomy tube changes with decreased error rates.

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.

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.