Transoral management of pharyngeal ballistics.

OBJECTIVE: To present a case of a ballistic foreign body in the pharynx after a gunshot wound to the maxillofacial area, an accompanying review of relevant literature, and our approach to management. METHOD: A 68-year-old male with no prior medical history presented to our trauma center with gunshot wounds to the left chin, left wrist, right chest, and sternum. A CT Angiogram of the neck revealed a bullet fragment left neck and additional fragment adjacent to the L hypopharynx at the level of the hyoid. The patient was taken to the operating room for direct laryngoscopy with foreign body removal and esophagoscopy. RESULTS: We document our workup and successful surgical removal of the pharyngeal ballistic foreign body via our video abstract, compiling preoperative imaging, intraoperative imaging, and video. Literature review of the subject accompanying our video abstract highlights the extensive complications that can occur from a retained foreign body in this area, supporting surgical removal of the foreign body if safely possible. CONCLUSION: Given the demonstrated feasibility and success of endoscopic foreign body removal from the pharyngoepiglottic space, in addition to overwhelming support for removal in the literature we recommend surgical extraction of ballistic foreign bodies located in the upper aerodigestive tract in stable patients to avoid early and long-term complications that can impact swallowing function, airway stability and the vital structures contained within the neck.

Profound Sudden Sensorineural Hearing Loss in Hematologic Malignancy: A Case for Urgent Cochlear Implantation With Discussion and Systematic Review of the Literature.

OBJECTIVE: To perform a systematic review of sensorineural hearing loss (SNHL) in hematologic malignancy; to describe an illustrative case of urgent cochlear implantation for bilateral profound SNHL and vestibular hypofunction in hyperviscosity syndrome; to suggest an approach to management of hyperviscosity syndrome-associated deafness with cochlear implantation. DATA SOURCES: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, systematic search of PubMed and Embase databases was undertaken for articles detailing clinical information about SNHL caused directly by hematologic malignancies. RESULTS: A total of 37 studies from 1989 to 2020 were qualitatively reviewed, the majority of which were case studies or case series. Causes of hearing loss in hematologic malignancy were found to include hyperviscosity syndrome, labyrinthine hemorrhage, infiltration, and infection. Patients with profound SNHL in hematologic malignancies from hyperviscosity syndrome may be candidates for cochlear implantation, and are also at increased risk for cochlear ossification. We review previous cases for their diagnostic approach, treatment paradigm, and outcomes data, and propose an approach to management. CONCLUSION: Bilateral sudden profound SNHL and vestibular hypofunction is a presenting symptom of hyperviscosity syndrome in hematologic malignancy. Although this entity is rare and previous reports have suggested improvement in hearing with oncologic treatment, cases with profound hearing loss are unlikely to recover serviceable hearing. We advocate for early magnetic resonance imaging with attention to fluid signal in the inner ear and serial audiometric follow-up to guide clinical decisions. We advise early consideration for cochlear implantation.

Does Voice Therapy Improve Vocal Outcomes in Vocal Fold Atrophy?

OBJECTIVES: Vocal fold atrophy is increasingly identified in the geriatric population. Current literature shows varying outcomes with voice therapy. Our goal was to analyze multidimensional vocal outcomes of these patients who underwent voice therapy. Secondary aims included determining compliance and analyzing differences in patients who undergo surgery. METHODS: 197 patients with vocal fold atrophy were included and reviewed. Patients were categorized by treatment received. Patient-reported, perceptual, aerodynamic, and acoustic voice outcomes were analyzed before and after therapeutic intervention. Changes were calculated and significance determined using Wilcoxon signed-rank and rank-sum tests. RESULTS: 89(45%) received no therapy, 43(22%) incomplete therapy, 51(26%) complete therapy, 8(4%) surgery only, and 6(3%) therapy followed by surgery. Those who completed voice therapy showed significant improvement in voice related quality of life (VRQOL) (P = .0225), glottal function index (GFI) (P < .001), grade, roughness, breathiness, asthenia, strain (GRBAS) (P < .001), maximum phonation time (MPT) (P = .0081), and fundamental frequency in women (P = .0024). No significant changes were found in mean airflow. When comparing patients who underwent surgery versus voice therapy, statistically significant differences were present between pre-treatment VRQOL (P = .0269) and GFI (P = .0166). CONCLUSIONS: Only 29% of patients with vocal atrophy completed voice therapy when recommended. Within this patient cohort, voice therapy results in significant improvement in multidimensional voice outcomes. Patients with vocal atrophy that undergo surgical treatment differ from those treated with voice therapy alone in their pre-treatment patient-reported measures.

Trial Vocal Fold Injection Predicts Thyroplasty Outcomes in Nonparalytic Glottic Incompetence.

OBJECTIVES: Trial vocal fold injection (TVFI) may be used prior to permanent medialization when voice outcome is uncertain. We aimed to determine whether voice outcomes of TVFI are predictive of, or correlate with outcomes after type I Gore-Tex medialization thyroplasty (GMT) in patients with nonparalytic glottic incompetence (GI). METHODS: Thirty-five patients with nonparalytic GI who underwent TVFI followed by GMT were retrospectively reviewed. Change in voice-related quality of life (VRQOL) after TVFI was compared to change in VRQOL 3 to 9 months after GMT. Similar comparisons were made for change in glottal function index (GFI) and change in grade, roughness, breathiness, asthenia, and strain (GRBAS). Sample correlation coefficients were calculated. RESULTS: Change in VRQOL after TVFI showed good correlation with change in VRQOL after GMT, r = 0.55. Change in GFI after TVFI showed strong correlation with change in GFI after GMT, r = 0.74. Change in GRBAS after TVFI showed excellent correlation with change in GRBAS after GMT, r = 0.90. CONCLUSION: The TVFI is a useful tool in nonparalytic GI when outcomes from glottic closure procedures are not clear. Voice outcome measures after TVFI strongly correlate with outcomes from GMT. These data may be used to more confidently counsel patients regarding their predicted outcomes of permanent medialization.

Identification of a p53-based portable degron based on the MDM2-p53 binding region.

In recent years the ubiquitin proteasome system (UPS) has garnered increasing interest as a target for chemotherapeutics. Due to the success of the proteasome inhibitors Bortezomib and Carfilzomib in the treatment of multiple myeloma, several new compounds have been developed to target E3 ubiquitin ligases and the proteasome in numerous human cancers. This has increased the need for new analytical methods to precisely measure intracellular enzyme activity in cells. A key component of a desired analytical method is a substrate that is capable of rapid intracellular ubiquitination yet easily incorporated into the next generation of more sophisticated UPS reporters. Portable degradation sequences, or degrons, have the ability to bind to E3 ligases and promote substrate ubiquitination when the sequence is presented in isolation or appended to other entities such as fluorescent peptide-based reporters. Previous work identified an E3 ligase (MDM2)-binding element at p53 amino acids 92-112, which was later demonstrated to be rapidly ubiquitinated in cytosolic lysates effectively functioning as a transportable degron. In this work, a shortened p53 sequence within amino acids 92-112 that displayed rapid ubiquitination kinetics was identified. A nine-member peptide library was synthesized using sequence elements of various sizes and lengths, all based on the initial 22 amino acid long sequence, containing a single ubiquitination site lysine. The ubiquitination kinetics were determined using a combination of gel electrophoresis and analytical high performance liquid chromatography (HPLC) to rank the members of the library and identify the optimal ubiquitination sequence. This analysis identified the five amino acid sequence, KGSYG, corresponding to residues 105-108 with an added N-terminal lysine, as a portable degron since this sequence demonstrated the most rapid ubiquitination kinetics.

A comparative analysis of the ubiquitination kinetics of multiple degrons to identify an ideal targeting sequence for a proteasome reporter.

The ubiquitin proteasome system (UPS) is the primary pathway responsible for the recognition and degradation of misfolded, damaged, or tightly regulated proteins. The conjugation of a polyubiquitin chain, or polyubiquitination, to a target protein requires an increasingly diverse cascade of enzymes culminating with the E3 ubiquitin ligases. Protein recognition by an E3 ligase occurs through a specific sequence of amino acids, termed a degradation sequence or degron. Recently, degrons have been incorporated into novel reporters to monitor proteasome activity; however only a limited few degrons have successfully been incorporated into such reporters. The goal of this work was to evaluate the ubiquitination kinetics of a small library of portable degrons that could eventually be incorporated into novel single cell reporters to assess proteasome activity. After an intensive literary search, eight degrons were identified from proteins recognized by a variety of E3 ubiquitin ligases and incorporated into a four component degron-based substrate to comparatively calculate ubiquitination kinetics. The mechanism of placement of multiple ubiquitins on the different degron-based substrates was assessed by comparing the data to computational models incorporating first order reaction kinetics using either multi-monoubiquitination or polyubiquitination of the degron-based substrates. A subset of three degrons was further characterized to determine the importance of the location and proximity of the ubiquitination site lysine with respect to the degron. Ultimately, this work identified three candidate portable degrons that exhibit a higher rate of ubiquitination compared to peptidase-dependent degradation, a desired trait for a proteasomal targeting motif.