Faculty Bibliography

Thyroid carcinoma of follicular cell origin exists on a histopathologic and clinical spectrum. The authors focus on the category of tumors that fall between the very favorable well-differentiated thyroid carcinomas and the very unfavorable anaplastic thyroid carcinomas. These intermediately aggressive tumors include poorly differentiated thyroid carcinoma and the newly defined differentiated high-grade thyroid carcinoma. Both diagnoses require certain histopathologic requirements be met in order to accurately identify these tumors post-operatively. Management remains primarily surgical though adjunctive treatments such as molecular targeted therapies (eg, tyrosine kinase inhibitors) and differentiation therapy (to restore tumor response to radioactive iodine) are also becoming available.

OBJECTIVE:To examine patient characteristics that impact serial observation adherence among vestibular schwannoma (VS) patients. STUDY DESIGN/METHODS:Retrospective chart review. SETTING/METHODS:Single tertiary care center. METHODS:We selected for VS patients from 201 to 2020 who elected for serial observation as initial management. Patients under 18, with previous management, bilateral or intralabyrinthine VS, and neurofibromatosis type 2 were excluded. Demographics, tumor characteristics, and follow-up status were extracted. Single and multiple logistic regression was used to identify patient characteristics impacting follow-up. RESULTS:We identified 507 VS patients who chose serial observation as initial management. Most were female (56.0%), white (73.0%), and married (72.8%). The mean age was 59.3 and most had private insurance (56.4%). Median Charlson Comorbidity Index was 2.00. Mean pure tone audiometry (PTA) average was 41.7 Hz. Average tumor size was 9.04 mm. Of 507 patients, 358 (70.6%) returned for at least one follow-up. On multiple logistic regression analysis, patients with private insurance (odds ratio [OR]: 0.39, confidence interval [CI]: 0.22-0.68; P = .001), racial minority background (OR: 0.54, CI: 0.35-0.83; P = .005), worse PTA averages (OR: 0.99, CI: 0.98-1.00; P = .044), and older age at diagnosis (OR: 0.97, CI: 0.95-1.00; P = .038) were less likely to follow-up. CONCLUSION/CONCLUSIONS:Private health insurance, racial minority background, worse PTA average, and older age were associated with decreased follow-up among adult VS patients electing serial observation. Patients with these characteristics may require additional support to ensure serial observation adherence.

Mature vertebrates maintain posture using vestibulospinal neurons that transform sensed in-stability into reflexive commands to spinal motor circuits. Postural stability improves across development. However, due to the complexity of terrestrial locomotion, vestibulospinal con-tributions to postural refinement in early life remain unexplored. Here we leveraged the relative simplicity of underwater locomotion to quantify the postural consequences of losing vestibulospinal neurons during development in larval zebrafish of undifferentiated sex. By comparing posture at two timepoints, we discovered that later lesions of vestibulospinal neu-rons led to greater instability. Analysis of thousands of individual swim bouts revealed that lesions disrupted movement timing and corrective reflexes without impacting swim kinemat-ics, and that this effect was particularly strong in older larvae. Using a generative model of swimming, we showed how these disruptions could account for the increased postural variability at both timepoints. Finally, late lesions disrupted the fin/trunk coordination observed in older larvae, linking vestibulospinal neurons to postural control schemes used to navigate in depth. Since later lesions were considerably more disruptive to postural sta-bility, we conclude that vestibulospinal contributions to balance increase as larvae mature. Vestibulospinal neurons are highly conserved across vertebrates; we therefore propose that they are a substrate for developmental improvements to postural control.Significance Statement Many animals experience balance improvements during early life. Mature vertebrates use vestibulospinal neurons to transform sensed instability into postural corrections. To under-stand if/how these neurons shape postural development, we ablated them at two develop-mentally important timepoints in larval zebrafish. Loss of vestibulospinal neurons disrupted specific stabilizing behaviors (swim timing, tilt correction, and fin/body coordination) more profoundly in older fish. We conclude that postural development happens in part by changes to vestibulospinal neurons - a significant step towards understanding how developing brains gain the ability to balance.

Neuronal responses during behavior are diverse, ranging from highly reliable 'classical' responses to irregular 'non-classically responsive' firing. While a continuum of response properties is observed across neural systems, little is known about the synaptic origins and contributions of diverse responses to network function, perception, and behavior. To capture the heterogeneous responses measured from auditory cortex of rodents performing a frequency recognition task, we use a novel task-performing spiking recurrent neural network incorporating spike-timing-dependent plasticity. Reliable and irregular units contribute differentially to task performance via output and recurrent connections, respectively. Excitatory plasticity shifts the response distribution while inhibition constrains its diversity. Together both improve task performance with full network engagement. The same local patterns of synaptic inputs predict spiking response properties of network units and auditory cortical neurons from in vivo whole-cell recordings during behavior. Thus, diverse neural responses contribute to network function and emerge from synaptic plasticity rules.

OBJECTIVE:To compare salivary flow rates between females and males, before and after radiation therapy (RT) for head and neck cancer (HNC). METHODS:Prospective observational multicenter cohort study (OraRad). Stimulated whole salivary flow was measured before RT and at 6 and 18 months after RT. RESULTS:Mean (95% confidence interval) salivary flow in g/min before RT was 0.81 (0.71, 0.90) in females (n = 107) and 1.20 (1.15, 1.25) in males (n = 391) (p < 0.001); at 6 months was 0.34 (0.24, 0.44) in females and 0.50 (0.44, 0.55) in males (p = 0.01); at 18 months was 0.49 (0.38, 0.59) in females and 0.70 (0.64, 0.75) in males (p < 0.001). Median nadir salivary flow after RT was 0.22 in females and 0.35 in males (p < 0.001). A lower nadir salivary flow in females, but not males, was associated with an increased risk for tooth failure (p = 0.02). CONCLUSIONS:Females with HNC have lower stimulated whole salivary flow than males, before and after RT. Low salivary flow after RT may be a risk factor for tooth failure among females. The lower pre-RT salivary flow rates in females, combined with prior literature in other populations, indicates that, in general, females have lower stimulated salivary flow than males.

Surveillance for survivors of head and neck cancer (HNC) is focused on early detection of recurrent or second primary malignancies. After initial restaging confirms disease-free status, the use of surveillance imaging for asymptomatic patients with HNC is controversial. Our objective was to comprehensively review literature pertaining to imaging and biomarker surveillance of asymptomatic patients treated for head and neck squamous cell carcinoma and to convene a multidisciplinary expert panel to provide appropriate use criteria for surveillance in representative clinical scenarios. The evidence base for the appropriate use criteria was gathered through a librarian-mediated search of literature published from 1990 to 2022 focused on surveillance imaging and circulating tumor-specific DNA for nonmetastatic head and neck squamous cell carcinoma using MEDLINE (Ovid), Embase, Web of Science Core Collection, and the Cochrane Central Register of Controlled Trials. The systematic review was reported according to PRISMA guidelines. Using the modified Delphi process, the expert panel voted on appropriate use criteria, providing recommendations for appropriate use of surveillance imaging and human papillomavirus (HPV) circulating tumor DNA. Of 5178 studies identified, 80 met inclusion criteria (5 meta-analyses/systematic reviews, 1 randomized control trial, 1 post hoc analysis, 25 prospective, and 48 retrospective cohort studies [with ≥50 patients]), reporting on 27,525 patients. No large, randomized, prospective trials examined whether asymptomatic patients who receive surveillance imaging or HPV circulating tumor DNA monitoring benefit from earlier detection of recurrence or second primary tumors in terms of disease-specific or quality-of-life outcomes. In the absence of prospective data, surveillance imaging for HNC survivors should rely on individualized recurrence-risk assessment accounting for initial disease staging, HPV disease status, and tobacco use history. There is an emerging surveillance role for circulating tumor biomarkers.

OBJECTIVES/UNASSIGNED:This study aims to synthesize current knowledge and outcomes related to pediatric auditory brainstem implantation (ABI) in children with severe inner ear malformations (IEMs). It highlights the clinical management practices, challenges, and potential future directions for consensus development in this field. METHODS/UNASSIGNED:A systematic review of findings presented at the Third International Pediatric ABI Symposium organized by the Hacettepe Cochlear Implant team between 3 and 5 September 2020 was conducted, incorporating data from 41 departments across 19 countries. Relevant clinical outcomes, imaging techniques, surgical approaches, and rehabilitation strategies were analyzed to identify key trends and variability in practices. RESULTS/UNASSIGNED:The review indicates that children receiving ABIs exhibit diverse auditory outcomes influenced by individual anatomical variations and developmental factors. Early implantation, particularly before the age of three, positively correlates with better auditory and language development. Multicenter experiences underscore the necessity of tailored decision-making, which considers both surgical candidacy and comprehensive rehabilitation resources. DISCUSSION:/UNASSIGNED:The variability in outcomes emphasizes the need for improved consensus and guidelines regarding eligibility, surgical techniques, and multidisciplinary rehabilitation approaches. Notable complications and the necessity for thorough imaging assessments were also identified as critical components affecting clinical decisions. CONCLUSION/UNASSIGNED:A formal consensus statement is warranted to standardize best practices in ABI management. This will not only enhance patient outcomes but also guide future research efforts to address the remaining challenges in the treatment of children with severe IEMs. Enhanced collaboration among team members will be pivotal in achieving these objectives.

OBJECTIVE:This study aimed to assess the impact of oral medicine (OM) practitioners on the literature regarding oral potentially malignant disorders (OPMDs), focusing on oral leukoplakia. STUDY DESIGN/METHODS:Using a bibliometric approach on the Scopus database until September 1, 2022, the top 100 cited articles were analyzed for article type, subtopic, specialty contributions, author metrics, and keywords. The Bibliometrix package for R and VOSviewer were used to evaluate interactions and generate science maps. RESULTS:OM practitioners, comprising 39% of contributors, played a significant role in studies related to nomenclature and screening of OPMDs. Notably, 4 OM specialists ranked among the most prolific authors, demonstrating denser collaboration with OM co-authors compared to other cancer specialists. However, there was a scarcity of OPMD management studies authored by OM practitioners. CONCLUSIONS:Despite the paucity of OM practitioners, the findings underscored the substantial contribution of OM practitioners in developing OPMD nomenclature and classification, emphasizing the need for increased collaboration with cancer specialists to conduct comprehensive clinical trials for OPMD management. The study highlights the importance of standardized criteria in OPMDs research for better data comparison and encourages further efforts from the OM scientific community.