Faculty Bibliography

The presence of tumor-induced systemic immune suppression, including lymphopenia, has been recognized in adult patients with glioblastoma for several decades, and pre-treatment neutrophil-to-lymphocyte count ratio (NLCR) is associated with inferior clinical outcome in patients with glioblastoma. Whether tumor-induced systemic immune suppression is also present in children with malignant brain tumors is not known. We performed a retrospective analysis of pretreatment neutrophil and lymphocyte counts in pediatric patients with medulloblastoma (MB) compared to a control group of children with posterior fossa pilocytic astrocytoma (PA). Compared to the control group, we observed statistically significantly lower absolute lymphocyte counts (ALCs) and higher NLCRs in the medulloblastoma group. Our findings suggest the presence of tumor-induced systemic immune suppression in MB patients already present at the time of diagnosis, with potential implications for the development of immune therapies in this population.

Walking is the predominant locomotor behavior expressed by land-dwelling vertebrates, but it is unknown when the neural circuits that are essential for limb control first appeared. Certain fish species display walking-like behaviors, raising the possibility that the underlying circuitry originated in primitive marine vertebrates. We show that the neural substrates of bipedalism are present in the little skate Leucoraja erinacea, whose common ancestor with tetrapods existed ∼420 million years ago. Leucoraja exhibits core features of tetrapod locomotor gaits, including left-right alternation and reciprocal extension-flexion of the pelvic fins. Leucoraja also deploys a remarkably conserved Hox transcription factor-dependent program that is essential for selective innervation of fin/limb muscle. This network encodes peripheral connectivity modules that are distinct from those used in axial muscle-based swimming and has apparently been diminished in most modern fish. These findings indicate that the circuits that are essential for walking evolved through adaptation of a genetic regulatory network shared by all vertebrates with paired appendages. VIDEO ABSTRACT.

While many of the basic tenants of upper lid blepharoplasty remain constant regardless of skin type, the thick-skinned eyelid patient requires special consideration. The brow may be naturally lower in the thick-skinned patient. These patients are more prone to having the brow pulled downward while attempting to remove redundant skin. There may also be more fat in the medial and central compartments. There may be fat in a lateral compartment overlying the lacrimal gland. Patient's expectations for a deep lid sulcus and complete excision of redundant skin may not be possible. They are more prone to an observable scar, a small dog ear at the lateral wound edge, and prolonged postoperative lid edema. Patients with lifelong upper lid fullness must get some input from significant others because their upper face aesthetic will change. In these patients, the eyelid surgery is not a rejuvenation, but a creation.

Motivation/UNASSIGNED:Shotgun DNA sequencing provides sensitive detection of all 182 HPV types in tissue and body fluid. However, existing computational methods either produce false positives misidentifying HPV types due to shared sequences among HPV, human, and prokaryotes, or produce false negative since they identify HPV by assembled contigs requiring large abundant of HPV reads. Results/UNASSIGNED:We designed HPViewer with two custom HPV reference databases masking simple repeats and homology sequences respectively and one homology distance matrix to hybridize these two databases. It directly identified HPV from short DNA reads rather than assembled contigs. Using 100,100 simulated samples, we revealed that HPViewer was robust for samples containing either high or low number of HPV reads. Using 12 shotgun sequencing samples from respiratory papillomatosis, HPViewer was equal to VirusTAP, and Vipie and better than HPVDetector with the respect to specificity and was the most sensitive method in the detection of HPV types 6 and 11. We demonstrated that contigs-based approaches had disadvantages of detection of HPV. In 1,573 sets of metagenomic data from 18 human body sites, HPViewer identified 104 types of HPV in a body-site associated pattern and 89 types of HPV co-occurring in one sample with other types of HPV. We demonstrated HPViewer was sensitive and specific for HPV detection in metagenomic data. Availability/UNASSIGNED:HPViewer can be accessed at https://github.com/yuhanH/HPViewer/. Contact/UNASSIGNED:Zhiheng.pei@nyumc.org. Supplementary information/UNASSIGNED:Supplementary data are available at Bioinformatics online.

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:Study the prevalence of otologic disease in a pediatric post-palatoplasty population with no prior ear tube placement in resource-deprived countries and assess patient characteristics associated with these abnormal results. DESIGN/METHODS:Retrospective data review. PARTICIPANTS/METHODS:Ecuadorian and Chinese children identified during humanitarian cleft lip and palate repair trips with cleft palates undergoing palatoplasty from 2007 to 2010. INTERVENTIONS/METHODS:Tympanometry and otoacoustic emission (OAE) testing performed following palatoplasty. Patients' parents administered surveys regarding perceived hearing deficits. MAIN OUTCOME MEASURES/METHODS:Age, gender, Veau classification, follow-up time, laterality, and country of origin were evaluated for possible association with type B tympanogram, "Refer" Otoacoustic results, and presence of hearing difficulty as identified by a parent. Significant predictors were further evaluated with multivariate analysis. RESULTS:The cohorts included 237 patients (129 Ecuadorian, 108 Chinese); mean age: 3.9 years; mean follow-up: 4.2 years. Thirty-nine percent scored type B, 38% failed OAE testing, and 8% of parents noted hearing deficits. The country of origin and a younger age were identified as predictive variables regarding type B tympanogram. Follow-up time, country of origin, and bilateral OAE "Refer" results all significantly predicted parental questionnaire results. Subsequent multivariable analysis further demonstrated effect modification between the 2 variables of age at palatoplasty and country of origin when predicting type B vs type A tympanometry. CONCLUSION/CONCLUSIONS:Without otologic intervention, cleft palate children in resource-deprived settings suffer type B tympanometry and failed OAE results with similar to increased incidences to other studied cleft palate populations with otologic interventions available.

Here, we describe a new method that allows localized proteomics of amyloid plaques and neurofibrillary tangles (NFTs), which are the two pathological hallmarks of Alzheimer's disease (AD). Amyloid plaques and NFTs are visualized using immunohistochemistry and microdissected from archived, formalin-fixed paraffin-embedded (FFPE) human tissue samples using laser-capture microdissection. The majority of human tissue specimens are FFPE; hence the use of this type of tissue is a particular advantage of this technique. Microdissected tissue samples are solubilized with formic acid and deparaffinized, reduced, alkylated, proteolytically digested, and desalted. The resulting protein content of plaques and NFTs is determined using label-free quantitative LC-MS. This results in the unbiased and simultaneous quantification of ~900 proteins in plaques and ~500 proteins in NFTs. This approach permits downstream pathway and network analysis, hence providing a comprehensive overview of pathological protein accumulation found in neuropathological features in AD.

Oral cavity squamous cell carcinoma (OCSCC) is the most common nonmelanoma head and neck cancer in the world, with an estimated 405 000 new cases expected each year. Subsites of the oral cavity include the alveolar ridge, buccal mucosa, anterior tongue, tonsillar pillar, retromolar trigone, hard palate, gingiva, and floor of the mouth. In this issue of the AHNS "Do you know your guidelines?" series, we review the evidence-based approach to the management of oral cavity carcinomas based on the framework provided by the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology.

OBJECTIVE:We aimed to characterize proliferative verrucous leukoplakia (PVL) from a clinical and histopathologic standpoint and suggest an updated classification. SUBJECTS AND METHODS/METHODS:Records of patients seen at three oral medicine centers with a clinical diagnosis of PVL were reviewed for clinical and histopathologic features, and malignant transformation (MT). RESULTS:There were 42 patients (median age: 69 years [range:36-88]; 35 females). 12.2% were current smokers. Family history of cancer was present in 43.7% of patients. Partial demarcation of lesion margins was present in 31.3% of lesions, followed by verrucous (27.5%), smooth (22.7%,) erythematous (22.3%), and fissured (18.3%) appearance. Large and contiguous, and multi-site and noncontiguous lesions, comprised 57.1% (24/42) and 35.7% (15/42) of PVL cases, respectively. 19.1% had prominent erythema (erythroleukoplakia). The most common histopathologic diagnosis at first visit was hyperkeratosis without dysplasia (22/42; 56.4%). MT occurred in 71.4% patients after a median of 37 months [range:1-210] from initial visit; erythroleukoplakia exhibited MT in 100% of cases. CONCLUSION/CONCLUSIONS:The generic term "proliferative leukoplakia (PL)" may be more appropriate than PVL because 18.3% were fissured and 22.7% erythematous. We also propose the term proliferative erythroleukoplakia to more accurately describe the subset of PL with prominent erythema, which had the highest MT rate.

Phantom electrode (PE) stimulation is achieved by simultaneously stimulating out-of-phase from two adjacent intra-cochlear electrodes with different amplitudes. If the basal electrode stimulates with a smaller amplitude than the apical electrode of the pair, the resulting electrical field is pushed away from the basal electrode producing a lower pitch. There is great interest in using PE stimulation in a processing strategy as it can be used to provide stimulation to regions of the cochlea located more apically than the most apical contact on the electrode array. The result is that even lower pitch sensations can be provided without additional risk of a deeper insertion. However, it is unknown if there are perceptual differences between monopolar (MP) and PE stimulation other than a shift in place pitch. Furthermore, it is unknown if the effect and magnitude of changing from MP to PE stimulation is dependent on electrode location. This study investigates the perceptual differences (including pitch and other sound quality differences) at multiple electrode positions using MP and PE stimulation using both a multidimensional scaling procedure (MDS) and a traditional scaling procedure. 10 Advanced Bionics users reported the perceptual distances between 5 single electrode (typically 1, 3, 5, 7, and 9) stimuli in either MP or PE (σ = 0.5) mode. Subjects were asked to report how perceptually different each pair of stimuli were using any perceived differences except loudness. Subsequently, each stimulus was presented in isolation and subjects scaled how "high" or how "clean" each sounded. Results from the MDS task suggest that perceptual differences between MP and PE stimulation can be explained by a single dimension. The traditional scaling suggests that the single dimension is place pitch. PE stimulation elicits lower pitch perceptions in all cochlear regions. Analysis of Cone Beam Computer Tomography (CBCT) data suggests that PE stimulation may be more effective at the apical part of the cochlea. PE stimulation can be used for new sound coding strategies in order to extend the pitch range for cochlear implant (CI) users without perceptual side effects.