Striatal network modeling in Huntington's Disease.

Medium spiny neurons (MSNs) comprise over 90% of cells in the striatum. In vivo MSNs display coherent burst firing cell assembly activity patterns, even though isolated MSNs do not burst fire intrinsically. This activity is important for the learning and execution of action sequences and is characteristically dysregulated in Huntington's Disease (HD). However, how dysregulation is caused by the various neural pathologies affecting MSNs in HD is unknown. Previous modeling work using simple cell models has shown that cell assembly activity patterns can emerge as a result of MSN inhibitory network interactions. Here, by directly estimating MSN network model parameters from single unit spiking data, we show that a network composed of much more physiologically detailed MSNs provides an excellent quantitative fit to wild type (WT) mouse spiking data, but only when network parameters are appropriate for the striatum. We find the WT MSN network is situated in a regime close to a transition from stable to strongly fluctuating network dynamics. This regime facilitates the generation of low-dimensional slowly varying coherent activity patterns and confers high sensitivity to variations in cortical driving. By re-estimating the model on HD spiking data we discover network parameter modifications are consistent across three very different types of HD mutant mouse models (YAC128, Q175, R6/2). In striking agreement with the known pathophysiology we find feedforward excitatory drive is reduced in HD compared to WT mice, while recurrent inhibition also shows phenotype dependency. We show that these modifications shift the HD MSN network to a sub-optimal regime where higher dimensional incoherent rapidly fluctuating activity predominates. Our results provide insight into a diverse range of experimental findings in HD, including cognitive and motor symptoms, and may suggest new avenues for treatment.

Occult Nodal Metastases in Individuals with Clinically Node-Negative Salivary Gland Malignancies.

OBJECTIVES: Salivary gland malignancies comprise a heterogeneous group of pathologies, for which treatment of the clinically negative neck may vary depending on numerous factors. Herein we present data on occult nodal metastases (ONM) as well as survival and recurrence from a large series of cN0 salivary gland malignancies. METHODS: Retrospective chart review was conducted on 532 patients, with 389 patients with major salivary gland cancers and 143 patients with minor salivary gland cancers. Demographic and treatment data were included and rates of ONM, overall survival, local recurrence, regional recurrence, and distant recurrence were analyzed. RESULTS: We found that the overall rate of ONM for parotid was 27% (63/235), for submandibular/sublingual was 35% (18/52), and for minor was 15% (4/26). Analysis of ONM rate at each nodal level was also performed, finding higher rates of level IV and V ONM than prior studies. Submandibular/sublingual and minor salivary gland malignancies showed a predominance of ONMs at levels I-III. Our survival and recurrence rates were similar to those found in previous studies. CONCLUSION: Our data also demonstrate a predominance of ONM in levels I-III for submandibular/sublingual and minor salivary gland cancers, suggesting elective dissection in these levels. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:1705-1715, 2024.

Trends in Female Authorship in Major Journals of 3 Oncology Disciplines, 2002-2018.

Importance: Gender disparity exists among authors of the oncology literature. Objective: To quantify trends in authorship by gender within a comprehensive data set of Medline-indexed oncology articles in medical journals with high impact factors. Design, Setting, and Participants: This cross-sectional study used Medline citations to examine archives of research journals from 3 disciplines in the oncology literature. Authors from all oncology-related articles with Medical Subject Headings terms assigned from 2002 to 2018 from 13 general oncology/medicine, radiation oncology, and surgical journals were included for analysis, encompassing clinical trials, observational studies (excluding case reports), reviews, systematic reviews, meta-analyses, and all other published articles. Data were analyzed between April and May 2020. Exposures: Authors were assigned genders based on societal naming norms via third-party gender identification service Gender-API.com. This assignment was internally validated based on manually obtained publicly available data on the internet. Main Outcomes and Measures: Trend in female authorship over time while considering journal type, authorship position, and article type. Results: A total of 420 526 authors from 58 368 articles were found, of which 400 945 were assigned a gender based on their name. In total, 29.5% (95% CI, 29.4%-29.6%) of authors were identified as female, rising from 25.5% (95% CI, 24.7%-26.3%) in 2002 to 31.7% (95% CI, 31.2%-32.3%) in 2018. Each subgroup of primary article type by journal type saw a rise in female authorship over the studied period. For primary articles, last authors were less likely to be women than first authors, regardless of journal type, year, and primary article type (eg, general oncology: odds ratio [OR], 0.60; 95% CI, 0.52-0.69). For general oncology articles, women were less likely to be authors of clinical trials at each authorship position than authors at that respective position for observational studies (first, second, and last authors: OR, 0.58; 95% CI, 0.49-0.67; other authors: OR, 0.84; 95% CI, 0.79-0.89). This difference was not seen for radiation oncology or surgical oncology journals. Conclusions and Relevance: This cross-sectional study found that female authorship in oncology research literature has increased. However, there remains a dearth of female senior authors, and the overall rise in female authorship has not kept up with the rise in female oncology faculty.

Utility of Transnasal Humidified Rapid Insufflation Ventilatory Exchange for Microlaryngeal Surgery.

OBJECTIVE: Microlaryngeal surgery typically requires oxygenation and ventilation via either an endotracheal tube (ETT), jet ventilation (JV), or intermittent apnea with an ETT. Transnasal Humidified Rapid Insufflation Ventilatory Exchange (THRIVE) delivered by high flow nasal cannula has been reported as an alternative technique. This method of apneic oxygenation and ventilation allows for stable, unobstructed visualization of immobile laryngeal structures. We aim to describe the technique and characterize intraoperative parameters related to its safety. STUDY DESIGN: Case Series. METHODS: The electronic medical record was reviewed for patients who underwent microlaryngoscopy using THRIVE technique. Patient demographics, procedural details, operative parameters, and anesthesia records were reviewed. Descriptive statistics were reported. RESULTS: A total of 53 patients underwent microlaryngoscopy using THRIVE as the sole method of ventilation, with 62% female. Median age was 51 years, and median BMI was 25 kg/m2 . Most patients were ASA class 2, and most had a Mallampati score of 2. The most common surgical indications were subglottic stenosis, vocal fold lesions, and vocal fold paralysis. Median apnea time was 16 minutes. At the end of case, median end tidal CO2 was 50 mmHg, and median minimum SpO2 was 95. Six cases required supplementation of THRIVE with JV or tracheal intubation for sustained oxygen desaturation. There was an increase in end tidal CO2 of 0.844 mmHg/min of apneic time. CONCLUSIONS: THRIVE is a safe and effective technique for oxygenation and ventilation in microlaryngeal, non-laser surgery in appropriately selected patients. To ensure safety, back-up plans such as jet ventilation and microlaryngeal ETT should be available. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:587-591, 2021.