Faculty Bibliography

BACKGROUND AND OBJECTIVES/OBJECTIVE:Osteoarthritis (OA) of the knee affects the aging population and has an associated influence on the health care system. Rigorous studies evaluating radiofrequency ablation for OA-related knee pain are lacking. This study compared long-term clinical safety and effectiveness of cooled radiofrequency ablation (CRFA) with intra-articular steroid (IAS) injection in managing OA-related knee pain. METHODS:This is a prospective, multicenter, randomized trial with 151 subjects with chronic (≥6 months) knee pain that was unresponsive to conservative modalities. Knee pain (Numeric Rating Scale [NRS]), Oxford Knee Score, overall treatment effect (Global Perceived Effect), analgesic drug use, and adverse events were compared between CRFA and IAS cohorts at 1, 3, and 6 months after intervention. RESULTS:There were no differences in demographics between study groups. At 6 months, the CRFA group had more favorable outcomes in NRS: pain reduction 50% or greater: 74.1% versus 16.2%, P < 0.0001 (25.9% and 83.8% of these study cohorts, respectively, were nonresponders). Mean NRS score reduction was 4.9 ± 2.4 versus 1.3 ± 2.2, P < 0.0001; mean Oxford Knee Score was 35.7 ± 8.8 vs 22.4 ± 8.5, P < 0.0001; mean improved Global Perceived Effect was 91.4% vs 23.9%, P < 0.0001; and mean change in nonopioid medication use was CRFA > IAS (P = 0.02). There were no procedure-related serious adverse events. CONCLUSIONS:This study demonstrates that CRFA is an effective long-term therapeutic option for managing pain and improving physical function and quality of life for patients with painful knee OA when compared with IAS injection. CLINICAL TRIAL REGISTRATION/BACKGROUND:ClinicalTrials.gov (NCT02343003).

OBJECTIVE The incidence of brain metastases is increasing with improved systemic therapies, many of which have a limited impact on intracranial disease. Stereotactic radiosurgery (SRS) is a first-line management option for brain metastases. The purpose of this study was to determine if there is a threshold tumor size below which local control (LC) rates approach 100%, and to relate these findings to the use of routine surveillance brain imaging. METHODS From a prospective registry, 200 patients with 1237 brain metastases were identified who underwent SRS between December 2012 and May 2015. The median imaging follow-up duration was 7.9 months, and the median margin dose was 18 Gy. The maximal diameter and volume of tumors were measured. Histological analysis included 96 patients with non-small cell lung cancers (NSCLCs), 40 with melanoma, 35 with breast cancer, and 29 with other histologies. RESULTS Almost 50% of brain metastases were NSCLCs and commonly measured less than 6 mm in maximal diameter or 70 mm3 in volume. Thirty-three of 1237 tumors had local progression at a median of 8.8 months. The 1- and 2-year actuarial LC rates were 97% and 93%, respectively. LC of 100% was achieved for all intracranial metastases less than 100 mm3 in volume or 6 mm in diameter. Patients whose tumors at first SRS were less than 10 mm maximal diameter or a volume of 250 mm3 had improved overall survival. CONCLUSIONS SRS can achieve LC rates approaching 100% for subcentimeter metastases. The earlier initial detection and prompt treatment of small intracranial metastases may prevent the development of neurological symptoms and the need for resection, and improve overall survival. To identify tumors when they are small, routine surveillance brain imaging should be considered as part of the standard of care for lung, breast, and melanoma metastases. CLASSIFICATION OF EVIDENCE Type of question: prognostic; study design: retrospective cohort; evidence: Class II.

OBJECTIVES/HYPOTHESIS: To describe the distribution of recurrent respiratory papillomatosis (RRP) lesions across 21 laryngeal anatomic regions in previously untreated patients at initial presentation to provide insight regarding the natural history of RRP. STUDY DESIGN: Multi-institutional, retrospective case series. METHODS: Initial laryngoscopic examination videos of 83 previously untreated patients with adult-onset RRP were reviewed. Papilloma locations were recorded using a 21-region laryngeal schematic. Multivariate analyses by anatomic subsite were conducted for the entire population and for subgroups stratified by sex, age, and proton pump inhibitor (PPI) usage. Heat maps were generated, hierarchically color coding the anatomic distribution of disease. RESULTS: In this cohort, RRP was most likely to occur on the true vocal folds (TVFs) and anterior commissure (P < .0001, odds ratio [OR]: 7.02); within the TVFs, the membranous vocal folds (MVFs) were most likely to be affected (P < .0001, OR: 3.56). The cohort was predominantly male (80.7%); males had a higher average number of affected sites (P = .005) and were more likely to have lesions in any laryngeal subsite (P < .0001, OR: 2.88,) compared to females. PPI users were more likely than nonusers to have disease in any laryngeal subsite (P = .0037, OR: 1.62), particularly in the posterior and subglottic regions (P = .0061, OR: 2.53). Age was not correlated with lesion prevalence or distribution. CONCLUSIONS: In untreated patients presenting to three laryngology clinics, the MVFs were most likely to be affected by RRP. Males had more anatomic sites affected by papilloma than females. The influence of PPI use on RRP distribution warrants further investigation. LEVEL OF EVIDENCE: 4. Laryngoscope, 2017.

Oral potentially malignant disorders (OPMDs) refer to epithelial lesions and conditions with an increased risk for malignant transformation; oral leukoplakia is the most commonly encountered. Overall, OPMDs have a low risk for malignant transformation, yet the challenge is the difficulty to reliably identify and predict which patients with OPMDs are at the highest risk for malignant transformation. Future research is needed to elucidate the molecular aspects of OPMDs, to improve current diagnostic strategies, leading to personalized management.

OBJECTIVES: A postlingually implanted adult typically develops hearing with an intact auditory system, followed by periods of deafness (or near deafness) and adaptation to the implant. For an early implanted child whose brain is highly plastic, the auditory system matures with consistent input from a cochlear implant. It is likely that the auditory system of early implanted cochlear implant users is fundamentally different than postlingually implanted adults. The purpose of this study is to compare the basic psychophysical capabilities and limitations of these two populations on a spectral resolution task to determine potential effects of early deprivation and plasticity. DESIGN: Performance on a spectral resolution task (Spectral-temporally Modulated Ripple Test [SMRT]) was measured for 20 bilaterally implanted, prelingually deafened children (between 5 and 13 years of age) and 20 hearing children within the same age range. Additionally, 15 bilaterally implanted, postlingually deafened adults, and 10 hearing adults were tested on the same task. Cochlear implant users (adults and children) were tested bilaterally, and with each ear alone. Hearing listeners (adults and children) were tested with the unprocessed SMRT and with a vocoded version that simulates an 8-channel cochlear implant. RESULTS: For children with normal hearing, a positive correlation was found between age and SMRT score for both the unprocessed and vocoded versions. Older hearing children performed similarly to hearing adults in both the unprocessed and vocoded test conditions. However, for children with cochlear implants, no significant relationship was found between SMRT score and chronological age, age at implantation, or years of implant experience. Performance by children with cochlear implants was poorer than performance by cochlear implanted adults. It was also found that children implanted sequentially tended to have better scores with the first implant compared with the second implant. This difference was not observed for adults. An additional finding was that SMRT score was negatively correlated with age for adults with implants. CONCLUSIONS: Results from this study suggest that basic psychophysical capabilities of early implanted children and postlingually implanted adults differ when assessed in the sound field using their personal implant processors. Because spectral resolution does not improve with age for early implanted children, it seems likely that the sparse representation of the signal provided by a cochlear implant limits spectral resolution development. These results are supported by the finding that postlingually implanted adults, whose auditory systems matured before the onset of hearing loss, perform significantly better than early implanted children on the spectral resolution test.

Cochlear-implant users who have experienced both analog and pulsatile sound coding strategies often have strong preferences for the sound quality of one over the other. This suggests that analog and pulsatile stimulation may provide different information or sound quality to an implant listener. It has been well documented that many implant listeners both prefer and perform better with multichannel analog than multichannel pulsatile strategies, although the reasons for these differences remain unknown. Here, we examine the perceptual differences between analog and pulsatile stimulation on a single electrode. A multidimensional scaling task, analyzed across two dimensions, suggested that pulsatile stimulation was perceived to be considerably different from analog stimulation. Two associated tasks using single-dimensional scaling showed that analog stimulation was perceived to be less Clean on average than pulsatile stimulation and that the perceptual differences were not related to pitch. In a follow-up experiment, it was determined that the perceptual differences between analog and pulsatile stimulation were not dependent on the interpulse gap present in pulsatile stimulation. Although the results suggest that there is a large perceptual difference between analog and pulsatile stimulation, further work is needed to determine the nature of these differences.

The incidence of oral cancer in the United States is increasing, especially in young people and women. Patients with oral cancer report severe functional pain. Using a patient cohort accrued through the New York University Oral Cancer Center and immune-competent mouse models, we identify a sex difference in the prevalence and severity of oral cancer pain. A neutrophil-mediated endogenous analgesic mechanism is present in male mice with oral cancer. Local naloxone treatment potentiates cancer mediator-induced orofacial nociceptive behavior in male mice only. Tongues from male mice with oral cancer have significantly more infiltrating neutrophils compared to female mice with oral cancer. Neutrophils isolated from the cancer-induced inflammatory microenvironment express beta-endorphin and met-enkephalin. Furthermore, neutrophil depletion results in nociceptive behavior in male mice. These data suggest a role for sex-specific, immune cell-mediated endogenous analgesia in the treatment of oral cancer pain.