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Introduction/Aims: Disease or injury can cause neuromuscular changes to the larynx that can affect voice, breathing, and swallowing. Motor nerve conduction studies have had limited use in the study of laryngeal neurophysiology, despite their importance in other anatomic sites. The aim of this study was to explore the feasibility of performing recurrent laryngeal motor nerve conduction studies (rlMNCS) in a rat model. Methods: rlMNCS were performed in 15 rats under anesthesia. A bipolar stimulating electrode was placed on the recurrent laryngeal nerve (RLN) 5 mm below the cricoid cartilage. Via direct laryngoscopy, a recording electrode was placed transorally into the thyroarytenoid muscle. The RLN was maximally stimulated to determine the compound muscle action potential (CMAP). Three consecutive trials were averaged. Results: The mean stimulating threshold to the RLN to achieve a CMAP from the thyroarytenoid was 1.7 ± 0.6 mA. RLN stimulation caused a visible adductor twitch of the vocal fold in all animals. The mean negative amplitude was 2.0 ± 0.8 mV, and the total area was 1.0 ± 0.4 mV ms. The CMAP latency and negative duration were 1.0 ± 0.1 ms and 0.9 ± 0.2 ms, respectively. Discussion: rlMNCS are feasible and may be useful in understanding laryngeal neurophysiology with disease or injury. This work could provide a tractable animal model for studying and monitoring treatment of neuromuscular conditions affecting voice, breathing, and swallowing. [ABSTRACT FROM AUTHOR]

Introduction: The strength of glottic closure with recurrent laryngeal nerve (RLN) stimulation has been indirectly measured experimentally by determining the squeezing pressure on a balloon inserted between the vocal folds, termed laryngeal adductory pressure (LAP). In this study, we sought to measure glottic closing force (GCF) directly and compare these results to LAP measures obtained with identical stimulation parameters. Methods: In canines, a method for measuring GCF was developed in which a suture was looped through a lateral thyrotomy hole, around the vocal process and back, then attached to a force gauge. The RLN was maximally stimulated and GCF recorded. The LAP was then measured as previously described, using the same stimuli. This process was repeated at 9 stimulation frequencies in 10-Hz intervals from 20 to 100 Hz. The GCF and LAP were compared using Pearson's correlation coefficient (PCC). Results: Both sides were measured in 16 dogs, resulting in 32 data sets. The LAP measures were obtained at all frequencies, while GCF was obtained in 246 of 288 (85.4%) attempts. The maximum GCF for each dog typically occurred at 80 to 100 Hz and averaged 0.287 ± 0.106 newtons. Plotting GCF versus LAP for each hemilaryngeal preparation, the mean PCC was 0.932 ± .042 (range, 0.802-0.987). The mean PCC did not differ between control (n = 26) and postoperative (n = 6) hemilarynges. Conclusion: This method for measuring GCF appears valid. The high Pearson's correlation coefficient indicates strong covariance between GCF and LAP, demonstrating that they are both measures of the same physical property. The LAP is easier to perform and more consistently obtained. [ABSTRACT FROM AUTHOR]

Objective: To investigate the efficacy of a novel adductor muscle-releasing technique designed to decrease the force of vocal fold adduction, as a potential surgical therapy for patients with adductor spasmodic dysphonia (ADSD). Study Design: Experimental animal study. Methods: A canine laryngeal model was used to assess the acute and sustained efficacy of a lateral cricoarytenoid (LCA) muscle release. A total of 34 canine hemilaryngeal preparations were divided among 7 experimental groups. The LCA muscle was separated from its cricoid cartilage origin via an open, anterior, submucosal approach. The laryngeal adductory pressures (LAP) were assessed pre- and post-muscle release via direct recurrent laryngeal nerve stimulation. Measurements were repeated at 1.5, 3, or 6 months postoperatively. Another study evaluated release of the thyroarytenoid (TA) muscle from its thyroid cartilage origin. Results: Releasing the LCA muscle demonstrated a significant decrease in LAP acutely and was maintained at all 3 time points with the aid of a barrier (P < .05). Without the barrier, the LCA muscle reattached to the cricoid. Acute release of the TA muscle did not significantly decrease the LAP. Conclusions: The proposed LCA release procedure may provide patients with a permanent treatment option for ADSD. However, longer-term studies and human trials are needed. [ABSTRACT FROM AUTHOR]

The article presents a study which determines the effects of vincristine on the laryngeal adductor function of posterior cricoarytenoid (PCA) muscle following a recurrent laryngeal nerve (RLN) injury. The study uses canine animal as subject of the experiment. The study reveals that vincristine injection in PCA muscle blocks the antagonist muscle against synkinetic reinnervation.

Laryngeal dystonia is a potentially disabling task specific dystonia primarily affecting speech. The evaluation and diagnosis of laryngeal dystonia remain challenging, and often require a multi‐disciplinary approach, involving collaboration among speech language pathologists, neurologists and laryngologists (1–5). It is crucial to correctly differentiate between the types of laryngeal dystonia due to the distinct therapeutic approaches and responses to botulinum toxin therapy or speech therapy. For educational purposes, we have divided laryngeal dystonia into two main types: adductor and abductor dystonia. In this article, we describe a series of examination techniques that can assist movement disorders neurologists diagnosing this condition, and appropriately differentiating the most common forms of laryngeal dystonia. [ABSTRACT FROM AUTHOR]

We performed a retrospective chart review to examine and describe our clinical experience of use of the Lichtenberger technique to place silicone elastomer keels after lysis of existing webs or for prevention of webs following anterior commissure surgery in adults. Twenty-two patients were identified for inclusion, ranging in age from 24 to 80 years. For 18 patients with existing glottic webs, the surgical procedure involved laryngoscopy with complete lysis of the anterior glottic web by laser or sharp technique, followed by placement of a square of silicone elastomer that is sutured in place with the Lichtenberger needle holder and left in place for 3 to 5 weeks. The procedure was well tolerated, and successfully corrected the web in all but 2 cases. For 4 patients, the procedure was performed prophylactically at the time of anterior commissure surgery considered high-risk for web formation. The procedure does not require a tracheotomy, and patients can maintain a normal diet and have functional phonation while the keel is in place. This approach to treating anterior glottic webs offers several advantages over traditional open thyrotomy with keel placement and should be considered to treat or prevent anterior glottic webs. [ABSTRACT FROM AUTHOR]

Volatile elements have a fundamental role in the evolution of planets. But how budgets of volatiles were set in planets, and the nature and extent of volatile-depletion of planetary bodies during the earliest stages of Solar System formation remain poorly understood. The Moon is considered to be volatile-depleted and so it has been predicted that volatile loss should have fractionated stable isotopes of moderately volatile elements. One such element, zinc, exhibits strong isotopic fractionation during volatilization in planetary rocks, but is hardly fractionated during terrestrial igneous processes, making it a powerful tracer of the volatile histories of planets. Here we present high-precision zinc isotopic and abundance data which show that lunar magmatic rocks are enriched in the heavy isotopes of zinc and have lower zinc concentrations than terrestrial or Martian igneous rocks. Conversely, Earth and Mars have broadly chondritic zinc isotopic compositions. We show that these variations represent large-scale evaporation of zinc, most probably in the aftermath of the Moon-forming event, rather than small-scale evaporation processes during volcanism. Our results therefore represent evidence for volatile depletion of the Moon through evaporation, and are consistent with a giant impact origin for the Earth and Moon. [ABSTRACT FROM AUTHOR]

Abstract: The δ66Zn (permil deviation of the 66Zn/64Zn ratio from a terrestrial standard) values for a suite of 20 non-Antarctic HED (howardite–eucrite–diogenite) meteorites and one mesosiderite, and for eight Antarctic eucrites and diogenites, were measured in order to determine the role of volatization in the formation of their presumed parent body, the asteroid 4-Vesta. The 20 non-Antarctic HEDs had δ66Zn values that ranged from −2.0‰ to +1.67‰, with a mean value of −0.01±0.39‰ (2se); this range likely represents a small-scale heterogeneity due to brecciation induced by multiple impacts. The non-Antarctic eucrites (δ66Zn=+0.00±0.58‰ (2se), n =12) were isotopically the same as the diogenites (δ66Zn=−0.31±0.80‰ (2se), n =4), and the howardites (δ66Zn=+0.26±0.37‰ (2se), n =4). On average, non-Antarctic eucrite falls were isotopically heavier (+0.50‰) than non-Antarctic finds (−1.00‰). The Antarctic finds studied were all unbrecciated samples, and they were significantly heavier than the non-Antarctic samples with a δ66Zn range of +1.63‰ to +6.22‰ for four eucrites (mean, +4.32‰) and +0.94‰ to +1.60‰ for three diogenites (mean+1.23‰), excluding one anomalous sample, while their Zn concentration is significantly lower than the brecciated samples. These data suggest that the unbrecciated eucrites probably represent the eucritic crust shortly after differentiation and cooling of the parent asteroid, at which time volatization of lighter zinc isotopes led to an isotopically heavy crust. Early impact events caused the ejection of these unbrecciated meteorites, which were subsequently spared from brecciation caused by multiple additional impacts on the much larger Vesta. The range of δ66Zn values and Zn concentration for the brecciated HEDs in this study supports a major contribution to the Vestan surface by chondritic impactors (−1.30<δ66Zn<+0.76‰ for ordinary and carbonaceous chondrites). The anomalous eucrite PCA 82502 (δ66Zn=−7.75‰) is significantly isotopically lighter than the other HEDs and is the natural sample with the lightest Zn isotopic composition reported in the solar system to date. This meteorite most likely originated from a distinct parent body. [Copyright &y& Elsevier]

Abstract: Enstatite meteorites include the undifferentiated enstatite chondrites and the differentiated enstatite achondrites (aubrites). They are the most reduced group of all meteorites. The oxygen isotope compositions of both enstatite chondrites and aubrites plot along the terrestrial mass fractionation line, which suggests some genetic links between these meteorites and the Earth as well. For this study, we measured the Zn isotopic composition of 25 samples from the following groups: aubrites (main group and Shallowater), EL chondrites, EH chondrites and Happy Canyon (impact-melt breccia). We also analyzed the Zn isotopic composition and elemental abundance in separated phases (metal, silicates, and sulfides) of the EH4, EL3, and EL6 chondrites. The different groups of meteorites are isotopically distinct and give the following values (‰): aubrite main group (−7.08<δ66Zn<−0.37); EH3 chondrites (0.15<δ66Zn<0.31); EH4 chondrites (0.15<δ66Zn<0.27); EH5 chondrites (δ66Zn=0.27±0.09; n =1); EL3 chondrites (0.01<δ66Zn<0.63); the Shallowater aubrite (1.48<δ66Zn<2.36); EL6 chondrites (2.26<δ66Zn<7.35); and the impact-melt enstatite chondrite Happy Canyon (δ66Zn=0.37). The aubrite Peña Blanca Spring (δ66Zn=−7.04‰) and the EL6 North West Forrest (δ66Zn=7.35‰) are the isotopically lightest and heaviest samples, respectively, known so far in the Solar System. In comparison, the range of Zn isotopic composition of chondrites and terrestrial samples (−1.5<δ66Zn<1‰) is much smaller (). EH and EL3 chondrites have the same Zn isotopic composition as the Earth, which is another example of the isotopic similarity between Earth and enstatite chondrites. The Zn isotopic composition and abundance strongly support that the origin of the volatile element depletion between EL3 and EL6 chondrites is due to volatilization, probably during thermal metamorphism. Aubrites show strong elemental depletion in Zn compared to both EH and EL chondrites and they are enriched in light isotopes (δ66Zn down to −7.04‰). This is the opposite of what would be expected if Zn elemental depletion was due to evaporation, assuming the aubrites started with an enstatite chondrite-like Zn isotopic composition. Evaporation is therefore not responsible for volatile loss from aubrites. On Earth, Zn isotopes fractionate very little during igneous processes, while differentiated meteorites show only minimal Zn isotopic variability. It is therefore very unlikely that igneous processes can account for the large isotopic fractionation of Zn in aubrites. Condensation of an isotopically light vapor best explains Zn depletion and isotopically light Zn in these puzzling rocks. Mass balance suggests that this isotopically light vapor carries Zn lost by the EL6 parent body during thermal metamorphism and that aubrites evolved from an EL6-like parent body. Finally, Zn isotopes suggest that Shallowater and aubrites originate from distinct parent bodies. [Copyright &y& Elsevier]

Objectives: The intensity of muscle activity immediately following intramuscular botulinum toxin injection may affect the clinical efficacy of the injection. We tested this effect in patients w ho underwent botulinum toxin injections for adductor spasmodic dysphonia. Methods: Patients were studied over 3 to 5 injection cycles. Cycle 1 was the baseline control, cycle 2 was randomized between a 1-hour reading aloud task ("exercise") and a 24-hour period of complete voice rest. For cycle 3, the patient completed the task not performed in cycle 2. Patients who were willing to continue for cycles 4 and 5 repeated the experiment at one half the injection dosage. Efficacy was determined with a battery of voice recordings and clinical outcomes instruments administered via telephone at 2- to 4-week intervals. The primary outcome measure was the result of the Voice-Related Quality of Life (VRQOL) instrument. Results: Nine patients (8 women, 1 man) with a mean age of 60.8 years (range, 42 to 76 years) completed at least 3 injection cycles. The VRQOL results were significantly higher for cycles that followed the exercise task. The patients reported subjectively that these were some of the best injection cycles they had ever experienced. Some achieved equivalent results with the half-dose injection plus exercise. The VRQOL results after voice rest cycles were not significantly different from the patients' baseline cycles. Conclusions: These results support the conclusion that a period of intense vocalization immediately following laryngeal botulinum toxin injections improves the efficacy of the injection. Possible mechanisms are proposed. [ABSTRACT FROM AUTHOR]

Objectives: Anterior cervical spine procedures carry an inherent risk of recurrent laryngeal nerve (RLN) injury. Patients with persistent RLN paresis may be asymptomatic because of compensation from the opposite side. If such patients undergo an opposite-side anterior approach for revision surgery, they are at risk for a second RLN injury, creating the potential for bilateral vocal fold paresis and possible need for tracheotomy. A program of routine screening for laryngeal paresis was implemented for these patients. This retrospective study reviews the results of this screening process. Methods: Patients referred for preoperative laryngeal nerve screening were identified. Their charts were reviewed for the results of the videolaryngoscopic examination, and for any recommendations made based on the findings. Relevant history and other physical findings were recorded. Results: Fifty screening laryngeal examinations were performed in 47 patients, of whom 31(66%) had previously under- gone a single anterior cervical approach procedure, and 16 (34%) had undergone more than one. Thirteen of the examinations (26%) revealed abnormal laryngeal findings, including paresis or paralysis in 11 cases (22%), of which 5 were asymptomatic. The findings resulted in a recommendation of a cervical approach from the already-involved side. None of the revision procedures resulted in bilateral vocal fold paralysis. The risk of laryngeal nerve injury appears to increase as higher cervical levels are approached. Conclusions: Minimally symptomatic injuries of the laryngeal nerves from prior neck surgery create a potential serious risk of bilateral vocal fold paralysis with subsequent procedures. Preoperative laryngeal screening is a simple and effective method for reducing this risk. [ABSTRACT FROM AUTHOR]

Objectives: Endoscopic approaches for submucosal vocal fold surgery may limit the surgeon's ability to release scars or to precisely implant filler material such as fat. In 1999, Gray et al described the "minithyrotomy" approach to this region. Technical aspects of this important new technique, clinical indications, and early results are reviewed. Methods: We performed a retrospective review and compiled the data of the office records, clinical notes, and videostroboscopic examinations of all of the four authors' patients who underwent this procedure. Results: Twenty-one patients underwent 22 minithyrotomy procedures for vocal fold scarring (6), lateralizing scar following polytetrafluoroethylene removal or trauma (5), scar with radiation fibrosis (2), sulcus vocalis (2), or presbylarynx or bowing (6) — bilaterally in 14 operations and unilaterally in 8. There were 13 male patients and 8 female patients, with a mean age of 58.3 years (range, 22 to 87 years). The mean follow-up was 9.1 months (range, 1 to 46 months). After submucosal vocal fold exploration, autologous fat was implanted in 20 of the 21 patients. Postoperative videostroboscopy demonstrated improved mucosal pliability in 19 cases and improved glottal closure in 20 cases. Most patients noted voice improvement. Complications were minimal. Conclusions: Gray's minithyrotomy is a highly effective approach for treating vocal fold scar processes, bowing, sulcus vocalis, and, potentially, other conditions. [ABSTRACT FROM AUTHOR]

Objective: To describe a novel surgical therapy for the treatment of medically refractory neuropathic cough, in which carefully selected subjects undergo surgical transection of the internal branch of the superior laryngeal nerve (iSLN).Methods: Subjects with a diagnosis of neuropathic cough, who were not improved after two medication trials, underwent iSLN block with local anesthetic in the office. While anesthetized, they underwent provocative testing to determine whether the nerve block improved their symptoms; if so, a modified barium swallow study (MBSS) was performed to determine whether they still swallowed safely without supraglottic sensation. Those who passed this screening were offered operative iSLN transection. We retrospectively reviewed our results to date.Results: Six subjects (5 females, ages 46-71), with neuropathic cough symptoms for 2-15 years, passed the screening and underwent iSLN transection procedures. At a mean follow-up of 8.2 months, significant symptomatic relief was experienced by 5/6 subjects, with Cough Severity Index (CSI) scores averaging 34.83 ± 6.94 pre-op (range 36-40) and 15.5 ± 11.81 post-op (range 0-29) (p = 0.043). Operative time averaged 49 min (range 30-64). There were no major complications. No subjects experienced post-op aspiration problems.Conclusion: This preliminary data supports iSLN transection as a viable option for subjects with refractory neuropathic cough. Our screening algorithm identifies subjects that would be expected to improve with this procedure and confirms a safe swallow. [ABSTRACT FROM AUTHOR]

Simple Summary: In head and neck squamous cell carcinoma (HNSCC), a major challenge with treatments targeting the immune system is an incomplete understanding of rare immune cell subtypes. Several recent studies have explored these cell types, but these studies have not integrated cellular data with clinicopathologic or demographic features to place conclusions in an appropriate clinical context. We deconvolve transcriptomic data from HNSCC patients to infer proportions of immune cell subtypes and place these data in the context of demographic, clinical, pathologic, and genomic characteristics. Our analysis revealed a possible association of γδ T cells with poor survival in HNSCC and underscore the need to better understand the role of these rare cells in HNSCC, including whether the presence of γδ T cells may predict the need for adjuvant therapy. (1) Background: The role of rare immune cell subtypes in many solid tumors, chief among them head and neck squamous cell carcinoma (HNSCC), has not been well defined. The objective of this study was to assess the association between proportions of common and rare immune cell subtypes and survival outcomes in HNSCC. (2) Methods: In this cohort study, we utilized a deconvolution approach based on the CIBERSORT algorithm and the LM22 signature matrix to infer proportions of immune cell subtypes from 517 patients with untreated HPV-negative HNSCC from The Cancer Genome Atlas. We performed univariate and multivariable survival analysis, integrating immune cell proportions with clinical, pathologic, and genomic data. (3) Results: We reliably deconvolved 22 immune cell subtypes in most patients and found that the most common immune cell types were M0 macrophages, M2 macrophages, and memory resting CD4 T cells. In the multivariable analysis, we identified advanced N stage and the presence of γδ T cells as independently predictive of poorer survival. (4) Conclusions: We uncovered that γδ T cells in the tumor microenvironment were a negative predictor of survival among patients with untreated HNSCC. Our findings underscore the need to better understand the role of γδ T cells in HNSCC, including potential pro-tumorigenic mechanisms, and whether their presence may predict the need for alternative therapy approaches. [ABSTRACT FROM AUTHOR]

Introduction: Unilateral vocal fold paralysis (UVFP) without an identifiable cause is termed idiopathic unilateral vocal fold paralysis (IUVFP). Some authors have postulated that select cases of IUVFP have a viral etiology, but the causality has not been established. We set out to review institutional cases of IUVFP and determine if there is a correlation between upper respiratory infection symptoms and presentation of IUVFP. Methods: Cases of IUVFP were reviewed over a 10-year period (2002-2012). The history was investigated to review presenting symptoms. We specifically reviewed for symptoms of upper respiratory infection at the onset of UVFP and tallied the frequency. Symptoms included sore throat, laryngitis, cough, influenza, bronchitis, pneumonia, otalgia, and sinusitis. The seasonal onset (if possible) was determined based on the history provided from the initial consultation. Study Design: Case series. Results: Overall, 107 patients presented with IUVFP; 35.5% of patients reported symptoms of upper respiratory infection at the onset of UVFP. Among these individuals, pharyngitis/laryngitis was the most common presenting symptom; 34.2% reported cough. In total, 40.0% of patients with IUVFP reported an onset of symptoms between December and February. Conclusions: This study suggests that symptoms of upper respiratory infection frequently occur with the presentation of IUVFP. The onset of symptoms tended to occur between December and February. The mechanism of viral-mediated UVFP has not been established. Future studies to explore this pathophysiology are needed. [ABSTRACT FROM AUTHOR]

Objective: Vocal fold paralysis is caused by injury to the recurrent laryngeal nerve (RLN). Current clinical measures of laryngeal innervation are often nonquantitative. Compound motor action potentials (CMAP) measure motor innervation. The goal of this study was to determine whether CMAP can quantify laryngeal innervation following acute nerve injury. Study Design: Animal study. Methods: Twelve canine hemilaryngeal preparations were used. The RLN was serially stimulated with increasing intensities until the nerve was maximally stimulated. The CMAP amplitude was measured for each intensity stimulation and correlated. Next, the RLN was incompletely transected, and the reduction in CMAP amplitude was correlated to the percentage of transected axons. The percentage of transected axons was determined using horseradish peroxidase (HRP) staining. Results: Combining all hemilaryngeal preparations, the submaximal stimulation of the RLN linearly correlated with the resultant CMAP amplitude (r = 0.83; 95% CI, 0.76-0.88). Following partial RLN transection, the percentage of remaining axons linearly correlated with the CMAP amplitude (r = 0.87; 95% CI, 0.34-0.98). Conclusions: CMAP amplitude is a quantitative measure that may correlate with the degree of vocal fold innervation in canines. Following RLN injury, CMAP may help clinicians quantify the number of intact axons, assess the likelihood of recovery, and counsel patients on their prognosis. [ABSTRACT FROM AUTHOR]

Background: HPV‐related oropharyngeal squamous cell carcinoma (OPSCC) is associated with a favorable prognosis, yet patients of color and low socioeconomic status (SES) continue to experience inferior outcomes. We aim to understand how the emergence of HPV has impacted race and SES survival disparities in OPSCC. Methods: A retrospective cohort of 18,362 OPSCC cases from 2010 to 2017 was assembled using the SEER (Surveillance, Epidemiology, and End Results) database. Cox proportional regression and Fine and Gray regression models were used to calculate hazard ratios (HRs) adjusting for race, SES, age, subsite, stage, and treatment. Results: Black patients had lower overall survival than patients of other races in HPV‐positive and HPV‐negative OPSCC (HR 1.31, 95% CI 1.13–1.53 and HR 1.23, 95% CI 1.09–1.39, respectively). Higher SES was associated with improved survival in all patients. Race had a diminished association with survival among high SES patients. Low SES Black patients had considerably worse survival than low SES patients of other races. Conclusion: Race and SES interact variably across cohorts. High SES was protective of the negative effects of race, although there remains a disparity in outcomes among Black and non‐Black patients, even in high SES populations. The persistence of survival disparities suggests that the HPV epidemic has not improved outcomes equally across all demographic groups. [ABSTRACT FROM AUTHOR]

Objectives: This study was performed to investigate the muscle-nerve-muscle reinnervation technique in the larynx, in which a nerve conduit implanted into an innervated muscle conducts axonal sprouting into a denervated muscle while maintaining function of the donor muscle. Methods: In this study, the muscle-nerve-muscle technique was used to direct superior laryngeal nerve axons to reinnervate intrinsic laryngeal muscles by implanting the recurrent laryngeal nerve stump into the cricothyroid muscle in 8 dogs. In 4 of the dogs, the recurrent laryngeal nerve trunk to the adductor muscles was divided so that all axonal sprouting was directed to the posterior cricoarytenoid muscle. Six-month electromyography data were obtained from 6 of the 8 dogs. Results: All 6 dogs showed evidence of successful reinnervation of the thyroarytenoid or posterior cricoarytenoid muscles with action potentials that corresponded to spontaneous respiratory efforts, while the donor cricothyroid muscles retained their phasic contraction. These responses were obliterated when the recurrent laryngeal nerve conduit was divided. Histologic examination of the intrinsic laryngeal muscles demonstrated successful reinnervation. Conclusions: The results confirm that intrinsic laryngeal muscles may be successfully reinnervated by the superior laryngeal nerve with the muscle-nerve-muscle technique, without sacrifice of function of the cricothyroid muscle. This method offers an alternative source of appropriately firing axons for laryngeal reinnervation procedures. [ABSTRACT FROM AUTHOR]

• Merkel cell carcinoma (MCC) often presents with regional lymph node involvement. • Indications for regional lymph node radiotherapy (rLN-RT) aren't well established. • rLN-RT reduced regional and distant relapse and improved disease-specific survival. • Adjuvant nodal radiation therapy (AnRT) improved all outcome-related endpoints. • Patients with ENE, ≥2 positive nodes, or bulky nodes benefited the most from AnRT. One-third of patients with Merkel cell carcinoma (MCC) present with locally advanced disease involving the regional lymph nodes, but indications for regional lymph node radiation therapy (rLN-RT) are not well established. 72 patients with locally advanced MCC were retrospectively reviewed. Regional lymph nodes were addressed with observation, lymph node dissection (LND) alone, definitive nodal radiotherapy (DnRT), or LND plus adjuvant nodal radiotherapy (AnRT). Cox regression was used to compare treatment modalities in terms of regional recurrence-free survival (RRFS), distant recurrence-free survival (DRFS), disease-free survival (DFS) and disease-specific survival (DSS). rLN-RT, including both DnRT and AnRT, improved RRFS (Hazard ratio (HR): 0.07, 95% confidence interval (CI): 0.01–0.40, p = 0.003), DRFS (HR: 0.28, CI: 0.11–0.76, p = 0.01), DFS (HR: 0.23, CI: 0.09–0.58, p = 0.002), and DSS (HR: 0.23, CI: 0.06–0.90, p = 0.03). AnRT improved DFS and DSS in high-risk subgroups (e.g., extranodal extension (ENE), ≥ 2 positive lymph nodes, or bulkier lymph nodes). The benefit of AnRT increased with higher disease burden. After controlling for these adverse factors, AnRT significantly improved RRFS (HR: 0.04, CI: 0.01–0.37, p = 0.004), DRFS (HR: 0.14, CI: 0.04–0.50, p = 0.003), DFS (HR: 0.09, CI: 0.02–0.33, p < 0.001), and DSS (HR: 0.21, CI: 0.05–0.89, p = 0.03). rLN-RT, including both DnRT and AnRT, reduces relapse and death from MCC in patients with node-positive disease. AnRT is particularly beneficial for patients with ENE, multiple involved lymph nodes, or larger nodal foci of disease. These results argue for more liberal use of nodal RT for MCC patients who present with node-positive disease. [ABSTRACT FROM AUTHOR]

Objectives: To explore the effect of incorporating cetuximab into induction chemotherapy in locally advanced head and neck squamous cell carcinoma (HNSCC).Materials and Methods: Retrospective comparative analysis of two consecutive prospective phase II trials was performed: trial 1 with nab-paclitaxel/cisplatin/5-FU and cetuximab (APF-C; n=30) and trial 2 with APF (n=30). Patients were scheduled to receive chemoradiation therapy (CRT) with cisplatin. T2-4 classification oropharynx (OP)/larynx/hypopharynx SCC were included. Cumulative incidence of death of disease (CIDD), overall survival (OS), and cumulative incidence of relapse were compared between APF-C and APF.Results: No significant differences in patient or tumor characteristics were noted between the groups. Median follow-up of surviving patients was 52 (25-95) months. Relapse occurred in 5 (17%) patients treated with APF-C and in 2 (7%) treated with APF (p=0.37). In human papillomavirus (HPV)-related OPSCC (n=34), the CIDD at 52months was 3.4% with APF-C and 2.6% with APF and the two-year OSs were 94%. In HPV-unrelated HNSCC (n=25), the CIDD at 52months was 4.4% with APF-C and 3.3% with APF and two-year OSs were 83% and 92%, respectively. CIDD or OS did not differ when stratified by treatment group and HPV status (CIDD: p=0.80; OS: p=0.30).Conclusion: This exploratory retrospective comparative analysis demonstrated no significant difference in CIDD, OS, or cumulative incidence of relapse between patients treated with APF-C or APF. [ABSTRACT FROM AUTHOR]

Objective: The compound motor action potential (CMAP) is the summated action potential from multiple muscle fibers activated by a single nerve impulse. The utility of laryngeal muscle CMAP for quantifying innervation following recurrent laryngeal nerve (RLN) injury was investigated. Method: In a series of 21 canine hemi-laryngeal preparations, RLNs were exposed and a stimulating electrode placed. Maximum CMAP amplitudes and area under the curve from the thyroarytenoid (TA) muscles were obtained at baseline and at 6 months following injury to the RLN. Injury mechanisms included crush, stretch, cautery, and complete transection with microsuture repair. Results: Prior to injury, baseline CMAP amplitudes and area under the curve were 15.81 mV and 15.49mVms, respectively. Six months following injury, CMAP amplitude and area under curve were 105.1% and 102.1% of baseline for stretch, 98.7% and 112.7% for crush, 93.3% and 114.3% for cautery. The CMAP amplitude and area under the curve in the transection/repair group had a 54.3% and 69.4% recovery, respectively, which were significantly different than baseline (P < .01, P < .05). These values were correlated with vocal fold motion. Conclusion: The CMAP is a measure of vocal fold innervation. The technique could be further developed for clinical and experimental applications. [ABSTRACT FROM AUTHOR]

Objectives/Hypothesis Development of an academic career easily follows a clinical course for which there are multiple role models; however, development of an academic research career involves few role models, and rarely do instructional guides reach out to the new faculty. The purpose of this article is to present the cumulative experiences of previously and currently funded authors to serve as a guide to young as well as older faculty for developing their research careers. Study Design Cumulative experiences of research-dedicated faculty. Methods This article is the result of lessons learned from developing a Triological Society National Physician-Scientist Program and Network, as well as the cumulative experiences of the authors. Results Table I illustrates key elements in developing a serious research career. Table II records the career courses of five surgeon-scientists, highlighting the continued theme focus with theme-specific publications and progressive grants. These cumulative experiences have face validity but have not been objectively tested. The value added is a composite of 50 years of experiences from authors committed to research career development for themselves and others. Conclusion Crucial elements in developing a research career are a desire for and commitment to high-quality research, a focus on an overall theme of progressive hypothesis-driven investigations, research guidance, a willingness to spend the time required, and an ability to learn from and withstand failure. Level of Evidence 5. [ABSTRACT FROM AUTHOR]

We previously reported that nab-paclitaxel-based induction chemotherapy ( IC) and concurrent chemoradiotherapy resulted in low relapse rates (13%) and excellent survival in head and neck squamous cell carcinoma ( HNSCC). We compare the disease-specific survival ( DSS) and overall survival ( OS) between patients given nab-paclitaxel, cisplatin, and fluorouracil with cetuximab ( APF-C) and historical controls given docetaxel, cisplatin, and fluorouracil with cetuximab ( TPF-C). Patients with locally advanced HNSCC were treated with APF-C ( n = 30) or TPF-C ( n = 38). After 3 cycles of IC, patients were scheduled to receive cisplatin concurrent with definitive radiotherapy. T and N classification and smoking history were similar between the two groups and within p16-positive and p16-negative subsets. The median duration of follow-up for living patients in the APF-C group was 43.5 (range: 30-58) months versus 52 (range: 13-84) months for TPF-C. The 2-year DSS for patients treated with APF-C was 96.7% [95% Confidence Interval ( CI): 85.2%, 99.8%] and with TPF-C was 77.6% ( CI: 62.6%, 89.7%) ( P = 0.0004). Disease progression that resulted in death was more frequent in the TPF-C group (39%) compared with the APF-C group (3%) when adjusted for competing risks of death from other causes (Gray's test, P = 0.0004). In p16 positive OPSCC, the 2-year DSS for APF-C was 100% and for TPF-C was 74.6% ( CI: 47.4%, 94.6%) ( P = 0.0019) and the 2-year OS for APF-C was 94.1% ( CI: 65.0%, 99.2%) and for TPF-C was 74.6% ( CI: 39.8%, 91.1%) ( P = 0.013). In p16 negative HNSCC, the 2-year DSS for APF-C was 91.7% ( CI: 67.6%, 99.6%) and for TPF-C was 82.6% ( CI: 64.4%, 94.8%) ( P = 0.092). A 2-year DSS and OS were significantly better with a nab-paclitaxel-based IC regimen ( APF-C) compared to a docetaxel-based IC regimen ( TPF-C) in p16-positive OPSCC. [ABSTRACT FROM AUTHOR]

Although coding variants in THAP1 have been causally associated with primary dystonia, the contribution of noncoding variants remains uncertain. Herein, we examine a previously identified Intron 1 variant (c.71+9C>A, rs200209986). Among 1672 subjects with mainly adult-onset primary dystonia, 12 harbored the variant in contrast to 1/1574 controls ( P < 0.01). Dystonia classification included cervical dystonia ( N = 3), laryngeal dystonia (adductor subtype, N = 3), jaw-opening oromandibular dystonia ( N = 1), blepharospasm ( N = 2), and unclassified ( N = 3). Age of dystonia onset ranged from 25 to 69 years (mean = 54 years). In comparison to controls with no identified THAP1 sequence variants, the c.71+9C>A variant was associated with an elevated ratio of Isoform 1 (NM_018105) to Isoform 2 (NM_199003) in leukocytes. In silico and minigene analyses indicated that c.71+9C>A alters THAP1 splicing. Lymphoblastoid cells harboring the c.71+9C>A variant showed extensive apoptosis with relatively fewer cells in the G2 phase of the cell cycle. Differentially expressed genes from lymphoblastoid cells revealed that the c.71+9C>A variant exerts effects on DNA synthesis, cell growth and proliferation, cell survival, and cytotoxicity. In aggregate, these data indicate that THAP1 c.71+9C>A is a risk factor for adult-onset primary dystonia. [ABSTRACT FROM AUTHOR]

To examine the iron (Fe) isotopic heterogeneities of CI and ordinary chondrites, we have analyzed several large chips (approximately 1 g) from three CI chondrites and three ordinary chondrites ( LL5, L5, and H5). The Fe isotope compositions of five different samples of Orgueil, one from Ivuna and one from Alais ( CI chondrites), are highly homogeneous. This new dataset provides a δ56Fe average of 0.02 ± 0.04‰ (2 SE, n = 7), which represents the best available value for the Fe isotopic composition of CI chondrites and probably the best estimate of the bulk solar system. We conclude that the homogeneity of CI chondrites reflects the initial Fe isotopic homogeneity of the well-mixed solar nebula. In contrast, larger (up to 0.26‰ in δ56Fe) isotopic variations have been found between separate approximately 1 g pieces of the same ordinary chondrite sample. The Fe isotope heterogeneities in ordinary chondrites appear to be controlled by the abundances of chondritic components, specifically chondrules, whose Fe isotope compositions have been fractionated by evaporation and recondensation during multiple heating events. [ABSTRACT FROM AUTHOR]

Background: Although the c.904_906delGAG mutation in Exon 5 of TOR1A typically manifests as early-onset generalized dystonia, DYT1 dystonia is genetically and clinically heterogeneous. Recently, another Exon 5 mutation (c.863G>A) has been associated with early-onset generalized dystonia and some ΔGAG mutation carriers present with late-onset focal dystonia. The aim of this study was to identify TOR1A Exon 5 mutations in a large cohort of subjects with mainly non-generalized primary dystonia. Methods: High resolution melting (HRM) was used to examine the entire TOR1A Exon 5 coding sequence in 1014 subjects with primary dystonia (422 spasmodic dysphonia, 285 cervical dystonia, 67 blepharospasm, 41 writer's cramp, 16 oromandibular dystonia, 38 other primary focal dystonia, 112 segmental dystonia, 16 multifocal dystonia, and 17 generalized dystonia) and 250 controls (150 neurologically normal and 100 with other movement disorders). Diagnostic sensitivity and specificity were evaluated in an additional 8 subjects with known ΔGAG DYT1 dystonia and 88 subjects with ΔGAG-negative dystonia. Results: HRM of TOR1A Exon 5 showed high (100%) diagnostic sensitivity and specificity. HRM was rapid and economical. HRM reliably differentiated the TOR1A ΔGAG and c.863G>A mutations. Melting curves were normal in 250/250 controls and 1012/1014 subjects with primary dystonia. The two subjects with shifted melting curves were found to harbor the classic ΔGAG deletion: 1) a non-Jewish Caucasian female with childhood-onset multifocal dystonia and 2) an Ashkenazi Jewish female with adolescent-onset spasmodic dysphonia. Conclusion: First, HRM is an inexpensive, diagnostically sensitive and specific, high-throughput method for mutation discovery. Second, Exon 5 mutations in TOR1A are rarely associated with non-generalized primary dystonia. [ABSTRACT FROM AUTHOR]

Adult-onset primary torsion dystonia (PTD) may spread to multiple body parts, but the relative risk of spread by site of onset of dystonia has not been well characterized. We retrospectively identified 602 patients with PTD out of 1,500 dystonia patients in our electronic database and extracted age at onset, site of onset, family history, and spread. Survival analyses were performed for groups based on site of onset, and hazard ratios compared relative risk of spread across groups. Patients with adult-onset blepharospasm were more likely to spread (31% past the head) than those with dystonia starting in the neck (9%), larynx (12%), or upper extremities (16%). Hazard ratios proved that the blepharospasm group had the greatest relative risk of spread. The rate of spread after onset varied significantly between the different groups. Most spread occurred in the first 1 to 2 years after onset of blepharospasm, whereas the risk of spread was relatively constant over time in cervical and laryngeal dystonia. Different sites of onset of PTD confer different risks of spread, important for clinical prognosis. Different risks of spread may provide clues about underlying pathogenesis of adult-onset primary dystonias. © 2006 Movement Disorder Society [ABSTRACT FROM AUTHOR]

Introduction: Delays in radiation are multifactorial, frequent, and associated with poor outcomes. This study investigates the effect of both primary and adjuvant radiation therapy duration and their interaction with other measures of treatment delay on survival in head and neck squamous cell carcinoma (HNSCC).Methods: We built a retrospective cohort using the National Cancer Database, consisting of primary oral cavity, hypopharynx, larynx and oropharynx squamous cell carcinoma without distant metastasis and with at least six weeks of radiation. The primary exposure was the duration of radiation therapy (DRT), and the primary outcome was death. We estimated the association between DRT and 5-year overall survival (OS) using Kaplan-Meier curves and hazard ratios (HRs) with Cox proportional hazard regression.Results: In both primary (definitive) and adjuvant (post-surgical) radiation settings, increased DRT results in decreased survival. In the primary radiation cohort, 5-year OS was 59.7% [59.1%-60.3%] among those with 47-53 days DRT, which decreased significantly with each subsequent week to completion (81+ days: 38.4% [36.2%-40.7%]). In the surgical cohort, survival decreased 16.5% when DRT extended beyond 75 days (40-46 days: 68.2% [67.3%-69.1%] vs. 75+ days: 53.3% [50.1%-56.7%]). Multivariate analyses showed increased hazard of death with increased DRT (primary radiation: 81+ days HR: 1.69 [1.58-1.81]); surgical: 75+ days HR: 1.61 [1.37-1.88]), with effects intensifying when restricting to those receiving full-dose radiation.Conclusion: A prolonged DRT was associated with worse OS in head and neck cancer. Radiation treatment delays of even a week lead to a significant survival disadvantage. DRT had a stronger association with survival than time to initiation of postoperative adjuvant radiotherapy. [ABSTRACT FROM AUTHOR]