Faculty Bibliography

BACKGROUND:Common in head and neck cancer patients, trismus can make speech and swallowing difficult and can compromise quality of life (QOL). Jaw range of motion exercise therapy may prevent or treat trismus in surgical patients. While the importance of these exercises is well-documented, there is little literature regarding the optimal timing of exercise initiation. METHODS:A prospective pilot study investigated the effects of early vs late jaw exercise intervention on postoperative jaw opening and QOL measures, which were examined descriptively. RESULTS:Timing of exercise intervention was not found to significantly impact the measured outcomes. However, provisional, descriptive findings showed that jaw opening was significantly associated with multiple QOL measures, with greater jaw opening associated with improved QOL. For certain QOL measures, this positive association was stronger at earlier time points than at later time points. CONCLUSIONS:The exploratory findings of this pilot study support further research into possible benefits of early jaw exercise intervention.

This article discusses complications that may occur after procedures on the lips, specifically focusing on injectable fillers. Evidence-based guidelines and suggested methods to manage these complications are presented in a systematic format.

OBJECTIVES/OBJECTIVE:The application of laser (light amplification by stimulated emission of radiation) energy in the larynx relies on thermal injury. The impact of this injury on adjacent tissue can be undesirable. Attempts have been made to limit the extent and range of injury to adjacent tissue. The O-Pel Surgical System (Precise Light Surgical, Inc., Campbell, CA), a new technology, utilizes kinetic energy through Pressure Induced Tissue Resection (PITR) (Precise Light Surgical, Inc.) to cut tissue, theoretically eliminating injury to adjacent tissue. The purpose of this study was to evaluate the PSL in canine vocal folds. METHODS:Four dogs underwent PITR incisions (4 mJ pulses at 200 Hz) on their vocal folds, through mucosa into the muscle. The animals were sacrificed at days 0, 3, 7, and 21 days postsurgery. The larynges were harvested and histology was performed with hematoxylin and eosin, Masson trichrome, and Verhoeff-van Gieson. RESULTS:At day 0, focal denudation of the epithelium and coagulation necrosis in the lamina propria and adjacent connective tissue are noted. On days 3 and 7, an inflammatory infiltrate of neutrophils is seen within the lamina propria and surrounding connective tissue with minimal edema and early deposition of collagen. At day 21, the mucosa is completely regenerated with the area of previous PITR into the muscle replaced with thick bundles of collagen. CONCLUSION/CONCLUSIONS:The unique PITR characteristics offer a potentially unique cutting technology for laryngeal microsurgery. The current canine study suggests appropriate and rapid healing. With refinements of the tip size of the probe and adjustment of energy, PITR will likely be an appropriate alternate to traditional lasers in laryngeal surgery. LEVEL OF EVIDENCE/METHODS:NA. Laryngoscope, 2019.

We introduce a real-time capable algorithm which estimates the long-term signal to noise ratio (SNR) of the speech in multi-talker babble noise. In real-time applications, long-term SNR is calculated over a sufficiently long moving frame of the noisy speech ending at the current time. The algorithm performs the real-time long-term SNR estimation by averaging "speech-likeness" values of multiple consecutive short-frames of the noisy speech which collectively form a long-frame with an adaptive length. The algorithm is calibrated to be insensitive to short-term fluctuations and transient changes in speech or noise level. However, it quickly responds to non-transient changes in long-term SNR by adjusting the duration of the long-frame on which the long-term SNR is measured. This ability is obtained by employing an event detector and adaptive frame duration. The event detector identifies non-transient changes of the long-term SNR and optimizes the duration of the long-frame accordingly. The algorithm was trained and tested for randomly generated speech samples corrupted with multi-talker babble. In addition to its ability to provide an adaptive long-term SNR estimation in a dynamic noisy situation, the evaluation results show that the algorithm outperforms the existing overall SNR estimation methods in multi-talker babble over a wide range of number of talkers and SNRs. The relatively low computational cost and the ability to update the estimated long-term SNR several times per second make this algorithm capable of operating in real-time speech processing applications.

BACKGROUND: While most hemangioblastomas (~70%) are sporadic and occur predominantly in the cerebellum, they may present as well as familial form associated with von Hippel-Lindau (VHL) syndrome, an autosomal dominant disorder caused by germline mutations of the VHL gene that trigger nuclear translocation of hypoxia-inducible factor (HIF)- 1alpha and angiogenesis. Although inactivation of VHL, a tumor suppressor gene, has been observed in hemangioblastomas, the underlying pathogenic mechanisms responsible for familial and sporadic hemangioblastomas remain incompletely understood.
METHOD(S): Whole exome sequencing of cerebellar hemangioblastoma tumors and matched blood leukocytes from 24 patients, age 24-63, was performed. After preparation and amplification of barcoded libraries, exomes were captured using Kapa Biosystems methodology and paired-end sequenced on Illumina HiSeq 2500 to an average 100-fold coverage. Following read alignment to hg19 genome, tumor and germline (leukocyte) sequences were compared, and pathogenic single nucleotide variants (SNVs) identified and validated by re-sequencing followed by pathway analysis. Additionally, tumor RNA isolated using Maxwell Promega was sequenced on Illumina instrument and the expression counts determined and normalized.
RESULT(S): We found 314 pathogenic and/or highly deleterious mutations (both germline and somatic) with a median of 13 mutations per patient. Five patients had VHL syndrome (germline VHL mutation) and 4 carried somatic VHL mutations. Among the VHL tumors, 82 mutations were identified, including HNF1B, NOTCH1 and TCF7L1, suggesting a potential contribution of altered RNA metabolism based upon pathway analysis. Among all hemangioblastomas, germline growth factor receptor variants (FGFR4 p.G388R (14/23 (61%) patients), IGF1R, PDGFRA and TYK2) known to activate STAT3 signaling and induce HIF-1alpha and angiogenesis, were identified. Non-hierarchical clustering of RNA sequencing data revealed two transcriptionally-distinct subtypes of hemangioblastomas.
CONCLUSION(S): Our findings indicate that hemangioblastomas can also occur by germline mutations known to activate STAT3 signaling, which may have significant implication in genetic testing and counseling of patients with hemangioblastomas

We present three adults with Down syndrome and obstructive sleep apnea (OSA) treated with hypoglossal nerve stimulation. The average age of these three males was 37.3 years. All patients had severe OSA on polysomnography. Postimplantation titration sleep studies exhibited residual OSA according to average total apnea-hypopnea index (AHI), but there were significant reductions (86%-100%) in the titrated AHI at the ideal device setting. Morbidity of the surgery was low, and there was excellent device adherence, with an average of 57.3 hours/week. All patients reported subjective improvements in symptoms, and one patient experienced improved blood sugar control. Laryngoscope, 2018.

BACKGROUND:Is posttreatment functional status prognostic of overall survival in patients with head and neck cancer (HNC). METHODS:In an HNC clinical trial, 495 patients had two posttreatment functional assessments measuring diet, public eating, and speech within 6 months. Patients were grouped by impairment (highly, moderately, modestly, or not impaired) and determined if they improved, declined, or did not change from the first assessment to the second. Multivariable Cox models estimated overall mortality. RESULTS:Across all three scales, the change in posttreatment patient function strongly predicted overall survival. In diet, patients who declined to highly impaired had three times the mortality of patients who were not impaired at both assessments (hazard ratio [HR] = 3.60; 95% confidence interval, 2.02-6.42). For patients improving from highly impaired, mortality was statistically similar to patients with no impairment (HR = 1.38; 95% CI, 0.82-2.31). CONCLUSIONS:Posttreatment functional status is a strong prognostic marker of survival in patients with HNC.

BACKGROUND:The aim of the study is to analyse the factors related to permanent surgical complications in children and adolescents with papillary thyroid carcinoma treated by total thyroidectomy with central and bilateral neck dissections. METHODS:Children and adolescents aged ≤18-year-old at presentation with papillary thyroid carcinoma during the years 1988-2010 underwent thyroid and lymph-node surgeries (with a median follow-up of 19.6 years) were analysed for post-surgical complications. RESULTS:Permanent surgical morbidity occurred in 14% (n = 70) of patients who underwent total thyroidectomy as well as bilateral central and lateral neck dissections (n = 509). Factors associated with permanent complications included pN1 with extra-nodal extension, > 4 metastatic lymph nodes in the central neck compartment, presence of distant metastases and younger age of patients at surgery. Patients who received extensive surgery had better relapse-free survival rates (p < 0.001). CONCLUSION/CONCLUSIONS:Total thyroidectomy and bilateral central as well as lateral neck dissections for children and adolescents with papillary thyroid carcinoma was associated with substantial postoperative complications. Nevertheless, it is associated with better prognosis for young patients with thyroid cancer. Prophylactic compartment-oriented lymph node dissections to these patients could be the management protocol in experienced hands.

Prior studies have reported high response rates with recombinant interferon-α (rIFN-α) therapy in patients with essential thrombocythemia (ET) and polycythemia vera (PV). To further define the role of rIFN-α, we investigated the outcomes of pegylated-rIFN-α2a (PEG) therapy in patients with ET/PV previously treated with hydroxyurea (HU). The Myeloproliferative Disorders Research Consortium (MPD-RC) 111 study was an investigator-initiated, international, multicenter, phase 2 trial evaluating the ability of PEG therapy to induce complete (CR) and partial (PR) hematologic responses in patients with high-risk ET/PV who were either refractory or intolerant to HU. The study included 65 patients with ET and 50 patients with PV. The overall response rate ORR (CR / PR) at 12 months was 69.2% (43.1% / 26.2%) in ET, and 60% (22%/38%) in PV patients. CR rates were higher in CALR mutated ET patients (56.5% vs. 28.0%, p= 0.01) as compared to subjects lacking a CALR mutation. The median absolute reduction in JAK2V617F variant allele fraction (VAF) was -6% (range -84%-47%) in patients achieving a CR versus +4% (range -18%-56%) in patients with PR/non-response (NR). Therapy was associated with a significant rate of adverse events (AE), most were manageable, and PEG discontinuation due to AEs occurred only in 13.9% of subjects. We conclude that PEG is an effective therapy for patients with ET/PV who were previously refractory and/or intolerant to HU. (ClinicalTrials.gov Identifier: NCT01259856).