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Processing stresses on therapeutic proteins may cause formation of subvisible particles. Different stress mechanisms generate particle populations with characteristic morphological "fingerprints," and machine learning techniques like convolutional neural networks (CNNs) allow classification of microscopy images of these particles according to known stresses at their root cause. Using CNNs to classify novel particle types not included during network training may lead to inaccurate classification, however, using CNNs to monitor the presence of particulate matter not explicitly used in training could serve as a useful process analytical technology. We used CNNs to classify and identify the root cause of particles generated by subjecting three monoclonal antibodies (mAbs) to various common manufacturing stresses. We probed the generality of particles generated by stressing different mAbs in different formulations and showed that CNN analyses were sensitive not only to the applied stress, but also the buffer conditions and the particular mAb that generated particle populations. Thus, models trained on images of particles created with one mAb and buffer system may not provide accurate root cause analysis when applied to particles generated by other mAb and buffer systems. A lever-rule analysis of CNN-derived fingerprints was used to characterize the composition of mixtures of particle types. Finally, we monitored the temporal evolution of CNN-derived fingerprints when novel populations of particles, which were not included during training, were generated by pumping mAb solutions through a peristaltic pump.

We aimed to establish an artificial intelligence (AI) model to identify parathyroid glands during endoscopic approaches and compare it with senior and junior surgeons' visual estimation.A total of 1,700 images of parathyroid glands from 166 endoscopic thyroidectomy videos were labeled. Data from 20 additional full-length videos were used as an independent external cohort. The YOLO V3, Faster R-CNN, and Cascade algorithms were used for deep learning, and the optimal algorithm was selected for independent external cohort analysis. Finally, the identification rate, initial recognition time, and tracking periods of PTAIR (Artificial Intelligence model for Parathyroid gland Recognition), junior surgeons, and senior surgeons were compared.The Faster R-CNN algorithm showed the best balance after optimizing the hyperparameters of each algorithm and was updated as PTAIR. The precision, recall rate, and F1 score of the PTAIR were 88.7%, 92.3%, and 90.5%, respectively. In the independent external cohort, the parathyroid identification rates of PTAIR, senior surgeons, and junior surgeons were 96.9%, 87.5%, and 71.9%, respectively. In addition, PTAIR recognized parathyroid glands 3.83 s ahead of the senior surgeons (p = 0.008), with a tracking period 62.82 s longer than the senior surgeons (p = 0.006).PTAIR can achieve earlier identification and full-time tracing under a particular training strategy. The identification rate of PTAIR is higher than that of junior surgeons and similar to that of senior surgeons. Such systems may have utility in improving surgical outcomes and also in accelerating the education of junior surgeons.3 Laryngoscope, 132:2516-2523, 2022.

After our coauthors described the first remote-access parathyroidectomy (RAP) series in 2000, several other approaches were developed. No systematic review has been performed to classify and evaluate RAP techniques. We performed a literature search using PubMed and Cochrane Library (CENTRAL). A total of 71 studies met our inclusion/exclusion criteria. RAP can be categorized into five approaches: (1) endoscopic and robotic axillary, (2) anterior chest, (3) transoral, (4) retroauricular, and (5) a combination of these approaches. The limited data in the literature suggest that the cure rates and safety of RAP are in no way inferior to those of open parathyroidectomy. Each approach has its advantages and disadvantages, and the recommendations for the selection of each approach are listed. The selection of approach methods might depend on the surgeon's experience and familiarity and the patient's preference and disease status.

To evaluate strategies to increase racial and ethnic diversity in the surgical workforce among trainees and faculty across surgical specialties.Embase, OVID/Medline, and Web of Science Core Collection.A review of US-based, peer-reviewed articles examining the effect of targeted strategies on racial and ethnic diversity in the surgical workforce was conducted from 2000 to 2020 with the PRISMA checklist and STROBE tool. Studies without an outlined strategy and associated outcomes were excluded. Eleven studies met inclusion criteria and were completed in general surgery, orthopaedic surgery, and otolaryngology-head and neck surgery.Efforts to increase exposure to surgery through internship programs and required clerkships with efforts to improve mentorship were common (6 of 11 [54.5%] and 3 of 11 [27.3%] studies, respectively). Three (27.3%) studies aimed to diversify the recruitment and selection process for the residency match and faculty hiring, and 2 (18.2%) aimed to increase representation among trainees, faculty, and leadership through holistic review processes paired with departmental commitment. Outcome metrics included surgical residency applications for individuals underrepresented in medicine, interview and match rates, faculty hiring, measures of a successful academic surgical career, and leadership representation. All strategies were successful in increasing diversity in the surgical workforce.A convincing yet limited body of literature exists to describe strategies and outcomes that address racial and ethnic diversity in the surgical workforce. While future inquiry is needed to move this field of interest forward, the evidence presented provides a framework for surgical residency programs/departments to develop approaches to increase racial and ethnic diversity.

Recurrent laryngeal nerve (RLN) invasion by thyroid carcinoma represents an advanced disease status with potentially significant co-morbidity.In a retrospective single-center study, we included patients with invaded RLNs operated on while using nerve monitoring techniques. We studied pre-, intra-, and postoperative parameters associated with postoperative vocal cord paralysis (VCP); 5-year recurrence-free survival (RFS); and 5-year overall survival (OS) in addition to two subgroup analyses of postoperative VCP in patients without preoperative VCP and based on source of RLN invasion.Of 65 patients with 66 nerves-at-risk, 39.3% reported preoperative voice complaints. Preoperative VCP was documented in 43.5%. The RLN was invaded by primary tumor in 59.3% and nodal metastasis in 30.5%. Papillary thyroid carcinoma was the most common pathologic subtype (80%). After 6 months, 81.8% had VCP. Complete tumor resection of the RLN was not associated with 5-year RFS (p = 0.24) or 5-year OS (p = 0.9). Resecting the RLN did not offer statistically significant benefit on 5-year RFS (p = 0.5) or 5-year OS (p = 0.38). Radioactive Iodine (RAI) administration was associated with improvement in 5-year RFS (p = 0.006) and 5-year OS (p = 0.004). Patients without preoperative VCP had higher IONM amplitude compared with patients with VCP. After a mean follow-up of 65.8 months, 35.9% of patients had distant metastases, whereas 36.4% had recurrence.Preoperative VCP accompanies less than half of patients with RLN invasion. Invaded RLNs may have existent electrophysiologic stimulability. Complete tumor resection and RLN resection were not associated with better 5-year RFS or OS, but postoperative RAI was.4 Laryngoscope, 132:2285-2292, 2022.

Papillary thyroid carcinoma (PTC) accounts for the majority of thyroid malignancies; risk of PTC recurrence over a 30-year period is approximately 30%, of which 70% occur as nodal metastases. Patients with nodal disease who are treated with therapeutic dissection are at higher risk for recurrence, but optimal nodal yield has not been defined. We aim to determine variables predictive of nodal recurrence of PTC within the first 5 years of surgery, with a focus on lymph node ratio (LNR), to inform clinical decision-making.Retrospective chart review identified 41 patients with nodal recurrence of PTC and 284 without nodal recurrence following thyroid surgery from 2000 to 2015. Cohorts were compared with regards to clinical history, surgical findings, and tumor characteristics.The fraction of the patients who underwent therapeutic central or lateral lymph node dissection was significantly higher in the nodal recurrence cohort. Maximum tumor size, presence of extrathyroidal extension, largest lymph node focus, LNR, postoperative thyroglobulin level, and administration of postoperative radioactive iodine were significantly increased in the PTC nodal recurrence group. LNR greater than 0.3 held the highest level of significance as a binary cutoff and captured the larger proportion of patients in the nodal recurrence cohort (68.3%).This study demonstrates characteristics to help assess risk of nodal recurrence of PTC and suggests LNR of lower than 0.3 is optimal to reduce risk of recurrence. The next steps include cohort studies to validate findings and weight variable analysis to optimize the extent of surgical therapeutic dissection.4 Laryngoscope, 132:1883-1887, 2022.

The widely used alkylating agent cyclophosphamide (CY) has substantive interpatient variability in the area under the curve (AUC) of it and its metabolites. Numerous factors may influence the drug-metabolizing enzymes that metabolize CY to 4-hydroxycyclophosphamide (4HCY), the principal precursor to CY's cytotoxic metabolite. We sought to identify endogenous metabolomics compounds (EMCs) associated with 4HCY formation clearance (ratio of 4HCY/CY AUC) using global metabolomics. Patients who undergo hematopoietic cell transplantation receiving post-transplant CY (PT-CY) were enrolled, cohort 1 (n = 26) and cohort 2 (n = 25) donating longitudinal blood samples before they started HCT (pre-HCT), before infusion of the donor allograft (pre-graft), before the first dose of PT-CY (pre-CY), and 24 h after the first dose of PT-CY (24-h post-CY), which is also immediately before the second dose of CY. A total of 512 and 498 EMCs were quantitated in two cohorts, respectively. Both univariate linear regression with false discovery rate (FDR), and pathway enrichment analyses using a global association test were performed. At the pre-CY time point, no EMCs were associated at FDR less than 0.1. At pre-HCT, cohort 1 had one EMC (levoglucosan) survive the FDR threshold. At pre-graft, cohort 1 and cohort 2 had 20 and 13 EMCs, respectively, exhibiting unadjusted p values less than 0.05, with the only EMCs having an FDR less than 0.1 being two unknown EMCs. At 24-h post-CY, there were three EMCs, two ketones, and threitol, at FDR less than 0.1 in cohort 2. These results demonstrate the potential of pharmacometabonomics, but future studies in larger samples are needed to optimize CY.

This study aimed to determine the perioperative surgical outcomes for head and neck cancer patients with cardiovascular diseases (CVDs).A cross-sectional analysis was performed using data from the Nationwide Readmissions Database between 2010 and 2014. Logistic regression analysis by enter and backward stepwise methods were used.A total of 8346 patients met the inclusion criteria. Patients with concomitant CVD had a higher frequency of complications (57.6%) compared with those without (47.4%) (odds ratio [OR] = 1.35, 95% confidence interval [CI] = 1.23-1.48, p 0.001). Patients with CVD comorbidities were prone to experience in-patient mortality at both admission (OR = 2.4, 95% CI = 1.42-4.05) and readmission (OR = 2.55, 95% CI = 1.10-5.87). CVD patients have prolonged hospital admission (OR = 1.14, 95% CI = 1.02-1.27, p = 0.020) and higher cost (OR = 1.28, 95% CI = 1.15-1.43, p 0.001). Patients with congestive heart failure were prone to 30 days readmission (OR = 1.67, 95% CI = 1.10-2.53, p = 0.019) and 90 days (OR = 1.65, 95% CI = 1.14-2.39, p = 0.010).This is the first study identifying factors predicting higher risk of perioperative complications of surgical management of head and neck cancer. Those with CVD had higher risk of adverse events.

Background Intraoperative neuromonitoring (IONM) techniques have evolved over the past decade into intermittent IONM (I-IONM) and continuous IONM (C-IONM) modes of application. Despite many prior publications on both types of IONM, there remains uncertainty about what outcomes should be measured for each form of IONM. The primary objective of this paper is to define categories of benefit for I-IONM/C-IONM and to clarify and standardize their reporting outcomes. Methods Expert review consensus statement utilizing modified Delphi methodology. Results I-IONM provides diagnosis, classification, and prevention of nerve injury through accurate and early nerve identification. C-IONM provides real-time information on nerve functional integrity and thus may prevent some types of nerve injury but cannot assist in nerve localization. Sudden mechanisms of nerve injury cannot be predicted or prevented by either technique. Conclusions I-IONM and C-IONM are complementary techniques. Future studies evaluating the utility of IONM should focus on outcomes that are appropriate to the type of IONM being utilized.

Most cases of thyroid carcinoma are classified as low risk. These lesions have been treated with open surgery, remote access thyroidectomy, active surveillance, and percutaneous ablation. However, there is lack of consensus and clear indications for a specific treatment selection. The objective of this study is to review the literature regarding the indications for management selection for low-risk carcinomas. Systematic review exploring inclusion and exclusion criteria used to select patients with low-risk carcinomas for treatment approaches. The search found 69 studies. The inclusion criteria most reported were nodule diameter and histopathological confirmation of the tumor type. The most common exclusions were lymph node metastasis and extra-thyroidal extension. There was significant heterogeneity among inclusion and exclusion criteria according to the analyzed therapeutic approach. Alternative therapeutic approaches in low-risk carcinomas can be cautiously considered. Open thyroidectomy remains the standard treatment against which all other approaches must be compared.

Genetic, symptomatic, and biochemical heterogeneity of patients with primary hyperparathyroidism (PHPT) has become apparent in recent years. An in-depth, evidence-based review of the phenotypes of PHPT was conducted. This review was intended to provide the resulting information to surgeons who operate on patients with hyperparathyroidism. This review revealed that the once relatively clear distinction between familial and sporadic PHPT has become more challenging by the finding of various germline mutations in patients with seemingly sporadic PHPT. On the one hand, the genetic and clinical characteristics of some syndromes in which PHPT is an important component are now better understood. On the other hand, knowledge is emerging about novel syndromes, such as the rare multiple endocrine neoplasia type IV (MEN4), in which PHPT occurs frequently. It also revealed that, currently, the classical array of symptoms of PHPT is seen rarely upon initial presentation for evaluation. More common are nonspecific, nonclassical symptoms and signs of PHPT. In areas of the world where serum calcium levels are checked routinely, most patients today are "asymptomatic" and they are diagnosed after an incidental finding of hypercalcemia; however, some of them have subclinical involvement of bones and kidneys, which is demonstrated on radiographs, ultrasound, and modern imaging techniques. Last, the review points out that there are three distinct biochemical phenotypes of PHPT. The classical phenotype in which calcium and parathyroid hormone levels are both elevated, and other disease presentations in which the serum levels of calcium or intact parathyroid hormone are normal. Today several, distinct phenotypes of the disease can be identified, and they have implications in the diagnostic evaluation and treatment of patients, as well as possible screening of relatives.

Objectives To determine the safety and efficacy of the conveyor cardiovascular system (CCS) to facilitate the delivery of large profile transcatheter valve devices. Background Transcatheter valve devices rely on force provided by the operator to be delivered to their intended position. This delivery may be challenging in a variety of anatomic scenarios. The ability to provide steering from the tip of the device by forming an arterial venous loop may help overcome these challenges. Methods Between May, 2019 and October, 2020, five patients were recruited for delivery of transcatheter valve devices with the CCS. These patients were deemed by the operators to have challenging anatomy which could make conventional valve delivery difficult or impossible. These patients were recruited as part of an FDA approved early feasibility study or through an institutional review board approved compassionate use protocol. Results Three patients underwent transcatheter mitral valve replacement with a SAPIEN-3 valve. One patient each underwent transcatheter aortic valve (TAVR) implantation with a SAPIEN 3 and 1 patient underwent TAVR implantation with a Lotus valve. All patients underwent successful implantation of the valve and removal of the CCS and valve delivery systems. There was no more than trivial mitral regurgitation post procedure in any patient and there was no more than trivial paravavular leak. There were no major in-hospital complications. Conclusions The CCS facilitates the delivery of large profile transcatheter valve devices in challenging anatomic scenarios. Further studies are needed with additional valve technologies.

Objective To evaluate the clinical value of intraoperative nerve monitoring (IONM) by comparing the procedure times for thyroidectomies performed with and without IONM. Methods A prospective, randomized, controlled study was conducted on 32 patients (representing 41 nerves at risk) undergoing thyroidectomies carried out by two experienced head and neck surgeons (CC & WP). Sixteen thyroidectomies were performed without IONM (the “non‐IONM group”), while 16 thyroidectomies were performed with IONM (the “IONM group”). The measured datapoints were setup time, time to visual identification of the recurrent laryngeal nerve (RLN), time to confirm the RLN electrophysiologically, dissection time, and total operative time. Results With both surgeons, the IONM group had shorter visual times to RLN identification than the non‐IONM group (CC: 3.7 minutes vs 5.3 minutes; WP: 3.4 minutes vs 9.7 minutes). Additionally, the electrophysiological identification time for the IONM group was shorter than the visual identification time for the non‐IONM group. The setup times, dissection times, and total operative times of the 2 groups did not significantly differ (P > .05). No RLN injuries were observed. Conclusions IONM reduces the time needed for RLN identification in thyroidectomies. Functional RLN confirmation can reassure surgeons of the operative results. Moreover, use of IONM does not significantly impact setup and total operative times. Level of evidence 2.

OBJECTIVES/HYPOTHESIS The objective was to identify whether injury of the external branch of the superior laryngeal nerve (EBSLN) or changes in EBSLN parameters after dissection during thyroidectomies correlate with changes in voice quality postoperatively. STUDY DESIGN Prospective multicenter case series. METHODS A prospective multicenter study was conducted on patients undergoing thyroidectomies with intraoperative nerve monitoring. Electromyography waveforms of EBSLN stimulation before (S1) and after superior pole dissection (S2) were evaluated using endotracheal tube (ETT) and cricothyroid intramuscular (CTM) electrodes. Voice outcomes were assessed using Voice-Related Quality of Life Surveys and Voice Handicap Index. RESULTS A total of 131 at-risk EBSLNs were evaluated in 80 patients. Two nerves showed loss of CTM twitch coupled with an absent S2 signal response. Complete EBSLN loss of signal was more likely with: 1) Cernea EBSLN anatomic classification Type 2B; 2) with a longer distance from the sternothyroid muscle insertion site; and 3) with larger lobar volumes (P

OBJECTIVES To provide a clinical disease state review of recent relevant literature and to generate expert consensus statements regarding the breadth of pediatric thyroid cancer diagnosis and care, with an emphasis on thyroid surgery. To generate expert statements to educate pediatric practitioners on the state-of-the-art practices and the value of surgical experience in the management of this unusual and challenging disease in children. METHODS A literature search was conducted and statements were constructed and subjected to a modified Delphi process to measure the consensus of the expert author panel. The wording of statements, voting tabulation, and statistical analysis were overseen by a Delphi expert (J.J.S.). RESULTS Twenty-five consensus statements were created and subjected to a modified Delphi analysis to measure the strength of consensus of the expert author panel. All statements reached a level of consensus, and the majority of statements reached the highest level of consensus. CONCLUSION Pediatric thyroid cancer has many unique nuances, such as bulky cervical adenopathy on presentation, an increased incidence of diffuse sclerosing variant, and a longer potential lifespan to endure potential complications from treatment. Complications can be a burden to parents and patients alike. We suggest that optimal outcomes and decreased morbidity will come from the use of advanced imaging, diagnostic testing, and neural monitoring of patients treated at high-volume centers by high-volume surgeons.

Background Preoperative diagnosis of medullary thyroid carcinoma (MTC) is often difficult, given the poor sensitivity of fine-needle aspiration (FNA) cytology for MTC. This study investigates this issue and presents recommendations for improving preoperative diagnostic paradigms in MTC cases. Design/method Histopathologically confirmed MTC patients with preoperative cytologic assessment of index nodules were enrolled. FNA diagnosis, final pathology, and surgery details were collected. Results Out of 71 patients, 49 (69%) were diagnosed by FNA as either definitive MTC (35, 49%) or suspected MTC (14, 20%) and 22 (31%) patients had no indication of MTC on FNA. Conclusion In a tertiary-care setting, one-third of subjects had an FNA interpretation that did not suggest the possibility of MTC. The limitations of preoperative diagnosis are especially problematic for MTC as they can cause delayed or incomplete treatment. Additional testing is proposed to improve preoperative diagnosis and surgical care of MTC patients.

To provide a contemporary resource to update clinicians and researchers on the current state of assessment of patient preferences.Published studies and literature regarding patient preferences, evidence-based practice, and patient-centered management in otolaryngology.Patients make choices based on both physician input and their own preferences. These preferences are informed by personal values and attitudes, and they ideally result from a deliberative evaluation of the risks, benefits, and other outcomes pertaining to medical care. To date, rigorous evaluation of patient preferences for otolaryngologic conditions has not been integrated into clinical practice or research. This installment of the "Evidence-Based Medicine in Otolaryngology" series focuses on formal assessment of patient preferences and the optimal methods to determine them.Methods have been developed to optimize our understanding of patient preferences.Understanding these patient preferences may help promote an evidence-based approach to the care of individual patients.

Objective: To provide a resource to educate clinical decision makers about the analyses and models that can be employed to support data-driven choices. Data Sources: Published studies and literature regarding decision analysis, decision trees, and models used to support clinical decisions. Review Methods: Decision models provide insights into the evidence and its implications for those who make choices about clinical care and resource allocation. Decision models are designed to further our understanding and allow exploration of the common problems that we face, with parameters derived from the best available evidence. Analysis of these models demonstrates critical insights and uncertainties surrounding key problems via a readily interpretable yet quantitative format. This 11th installment of the Evidence-Based Medicine in Otolaryngology series thus provides a step-by-step introduction to decision models, their typical framework, and favored approaches to inform data-driven practice for patient-level decisions, as well as comparative assessments of proposed health interventions for larger populations. Conclusions: Information to support decisions may arise from tools such as decision trees, Markov models, microsimulation models, and dynamic transmission models. These data can help guide choices about competing or alternative approaches to health care. Implications for Practice: Methods have been developed to support decisions based on data. Understanding the related techniques may help promote an evidence-based approach to clinical management and policy.

Therapeutic proteins are exposed to numerous stresses during their manufacture, shipping, storage and administration to patients, causing them to aggregate and form particles through a variety of different mechanisms. These varied mechanisms generate particle populations with characteristic morphologies, creating “fingerprints” that are reflected in images recorded using flow imaging microscopy. Particle population fingerprints in test samples can be extracted and compared against those of particles produced under baseline conditions using an algorithm that combines machine learning tools such as convolutional neural networks with statistical tools such as nonparametric density estimation and Rosenblatt transform-based goodness-of-fit hypothesis testing. This analysis provides a quantitative method with user-specified Type 1 error rates to determine whether the mechanisms that produce particles in test samples differ from particle formation mechanisms operative under baseline conditions. As a demonstration, this algorithm was used to compare particles within intravenous immunoglobulin (IVIg) formulations that were exposed to freeze-thawing and shaking stresses within a variety of different containers. This analysis revealed that seemingly subtle differences in containers (e.g., glass vials from different manufacturers) generated distinguishable particle populations after the stresses were applied. This algorithm can be used to assess the impact of process and formulation changes on aggregation-related product instabilities.

Background Flexible fiberoptic laryngoscopy is performed prior to thyroid surgery to evaluate the function of the recurrent laryngeal nerve. We assess the cost-effectiveness of preoperative laryngoscopy prior to total thyroidectomy for a low-risk thyroid cancer patient without dysphonia. Methods A decision tree analysis was performed from a third-party payer perspective. We assessed the cost-effectiveness of fiberoptic laryngoscopy prior to total thyroidectomy for T2N0M0 papillary thyroid carcinoma, such that an ipsilateral vocal fold paralysis alters the surgical plan to hemi-thyroidectomy, when permissible, to avoid the risk of bilateral vocal fold paralysis. Results Performing preoperative laryngoscopy to assess vocal fold function has an incremental cost-effectiveness ratio (ICER) of 45 193 USD/QALY compared to no laryngoscopy. At a willingness-to-pay of 100 K/QALY, the intervention is cost-effective if the incidence of vocal fold paralysis is at least 0.57%, or when the permissible rate of hemithyroidectomy in cases of incidental paralysis is at least 41%. Probabilistic sensitivity analysis shows that laryngoscopy is cost-effective in 90.9% of cases. Conclusions Fiberoptic laryngoscopy is a cost-effective prior to total thyroidectomy in asymptomatic, low-risk thyroid cancer patients.

Objectives/hypothesis Recent American Thyroid Association Guidelines recommend either near-total/total thyroidectomy or lobectomy for patients with a thyroid nodule suspicious for papillary thyroid cancer (PTC) on fine-needle aspiration (FNA) biopsy (Bethesda V). In this analysis, we aim to assess the cost-effectiveness of lobectomy in comparison to total thyroidectomy. Study design Cost-effectiveness analysis. Methods A Markov model cost-effectiveness analysis was performed for a base case followed for 20 years postoperatively. Cost and probabilities data were retrieved from the current literature. Effectiveness was represented by quality-adjusted life year (QALY). Results Total thyroidectomy protocol produced an incremental cost of $2,681.36 and incremental effectiveness of -0.24 QALY as compared to lobectomy protocol (incremental cost-effectiveness ratio [ICER] = -$11,188.85/QALY). Sensitivity analysis demonstrated that total thyroidectomy becomes a cost-effective strategy only if the risk of stages III and IV PTC is 82.4% among patients with suspicious PTC on preoperative FNA. Lobectomy is cost effective and preferred over total thyroidectomy as long as lobectomy complications are less than 50%. Conclusions Total thyroidectomy is not just cost prohibitive but also associated with a lower effectiveness compared to lobectomy. Level of evidence 2c Laryngoscope, 2020.

OBJECTIVE To investigate intraoperative nerve monitoring (IONM) use among thyroid surgeons. METHODS A 25-question survey was used to assess attitudes regarding IONM use. Surveys were sent to surgeons registered to the American Academy of Otolaryngology-Head and Neck Surgery, International Association of Endocrine Surgeons, and American Head and Neck Society. RESULTS Among 1,015 respondents, 83% reported using IONM (65.1% always using IONM and 18.1% reporting selective use). For selective users, a majority reported using IONM for reoperative cases (95.1%) and in cases with preoperative vocal cord paralysis (59.8%). When comparing location, there was a significant difference in IONM implementation (P

Ansa-to-recurrent laryngeal nerve (ANSA-RLN) reinnervation procedures are now often first-line treatments for some children with unilateral vocal fold immobility. Although many describe that children with prolonged denervation and true vocal fold atrophy should not undergo this procedure, there has been no gold-standard means of identifying true denervation. Here, we describe a novel technique using evoked vagal electromyography to predict degree of chronic nerve injury prior to recurrent laryngeal nerve reinnervation in children. This is a simple, readily available technique that may play an important role in predicting likelihood of success with pediatric ANSA-RLN reinnervation. Laryngoscope, 130:747-751, 2020.

Health care consumer organizations and insurance companies increasingly are scrutinizing value when considering reimbursement policies for medical interventions. Recently, members of several American Academy of Otolaryngology-Head & Neck Surgery (AAO-HNS) committees worked closely with one insurance company to refine reimbursement policies for preoperative localization imaging in patients undergoing surgery for primary hyperparathyroidism. This endeavor led to an AAO-HNS parathyroid imaging consensus statement (https://www.entnet.org/content/parathyroid-imaging). The American Head and Neck Society Endocrine Surgery Section gathered an expert panel of authors to delineate imaging options for preoperative evaluation of surgical candidates with primary hyperparathyroidism. We review herein the current literature for preoperative parathyroid localization imaging, with discussion of efficacy, cost, and overall value. We recommend that planar sestamibi imaging, single photon emission computed tomography (SPECT), SPECT/CT, CT neck/mediastinum with contrast, MRI, and four dimensional CT (4D-CT) may be used in conjunction with high-resolution neck ultrasound to preoperatively localize pathologic parathyroid glands. PubMed literature on parathyroid imaging was reviewed through February 1, 2019.

Objectives/hypothesis The potential for brachial plexopathy due to arm positioning is a major concern regarding the robotic transaxillary approach. Intraoperative nerve monitoring via somatosensory evoked potential (SSEP) has been suggested to prevent such injury. In this study, we examined the use of SSEP in detecting imminent brachial plexus traction during robotic transaxillary thyroid and parathyroid surgery. Study design Retrospective case series. Methods A analysis was performed for all patients undergoing robotic transaxillary surgery with continuous intraoperative SSEP monitoring at a North American institution between 2015 and 2017. A significant intraoperative SSEP change was defined as a decrease in signal amplitude of >50% or an increase in latency of >10% from baseline established during preoperative positioning. Results One hundred thirty-seven robotic transaxillary surgeries using SSEP monitoring were performed on 123 patients. Seven patients (5.1%) developed significant changes, with an average SSEP amplitude reduction of 73% ± 12% recorded at the signals' nadir. Immediate arm repositioning resulted in recovery of signals and complete return to baseline parameters in 14.3 ± 9.2 minutes. There was no difference in age (40.4 ± 9.4 years vs. 44.5 ± 13.4 years; P = .31) or body mass index (27.3 ± 3.7 kg/m2 vs. 26.9 ± 6.1 kg/m2 ; P = .79) between cases with and without SSEP change. Operative time was shorter for patients with significant SSEP change (131.6 ± 14.7 minutes vs. 146.5 ± 46.7 minutes; P = .048). There were no postoperative positional brachial plexus injuries. Conclusions SSEP is a novel, safe, and reliable tool in detection of position-related brachial plexus neuropathy. Intraoperative monitoring using SSEP can play a vital role in early recognition and prevention of injury during robotic transaxillary thyroid and parathyroid surgery. Level of evidence 4 Laryngoscope, 129:2663-2668, 2019.

Background This American Head and Neck Society (AHNS) consensus statement focuses on evidence-based comprehensive pain management practices for thyroid and parathyroid surgery. Overutilization of opioids for postoperative pain management is a major contributing factor to the opioid addiction epidemic however evidence-based guidelines for pain management after routine head and neck endocrine procedures are lacking. Methods An expert panel was convened from the membership of the AHNS, its Endocrine Surgical Section, and ThyCa. An extensive literature review was performed, and recommendations addressing several pain management subtopics were constructed based on best available evidence. A modified Delphi survey was then utilized to evaluate group consensus of these statements. Conclusions This expert consensus provides evidence-based recommendations for effective postoperative pain management following head and neck endocrine procedures with a focus on limiting unnecessary use of opioid analgesics.

BACKGROUND We aim to audit our institution's opioid prescribing practices after common cervical procedures. METHODS Retrospective cohort study from one medical center. Reviewed records from 2016-2019 for 472 patients who underwent one of several common cervical procedures. Data collected on demographics, perioperative details, in-hospital pain medication use, and opioids prescribed at discharge. Multivariable logistic regression was run. RESULTS In hospital, median daily milligram morphine equivalents (MME) was 4 (IQR 0-15). Median MME prescribed at discharge was 112.5 MME (IQR 75-150). 3/472 patients received NSAIDs. Predictors of decreased discharge MME were age 70 and older (OR 0.33, p = 0.037) and more recent year (compared to 2016, OR 0.23 [p = 0.031] for 2017, OR 0.13 [p = 0.001] for 2018, and OR 0.070 [p

Objectives/Hypothesis During intraoperative neuromonitoring in thyroid surgery, two different kinds of stimulator probes, monopolar and bipolar, are commonly used to stimulate the laryngeal nerves. We explore the unique characteristics of both of these probes as they relate to intraoperative laryngeal nerve mapping. Methods Twenty-one patients undergoing neuromonitored thyroidectomy by a single surgeon were enrolled. Electromyography (EMG) amplitude and latency measurements were prospectively recorded concurrently from 1 mA stimulation of vagus nerve (VN) and inferior/superior recurrent laryngeal nerve before (with and without fascia) and after thyroid resection using bipolar and monopolar stimulator probes. Results Significantly higher amplitudes were obtained with monopolar stimulator probes as compared to bipolar probes, in several stimulation scenarios such as at right VN pre-resection (carotid sheath intact), right VN pre-resection (carotid sheath dissected), right VN post-resection and left VN (carotid sheath dissected). No significant differences were found between amplitudes and latency values in all other stimulation scenarios. Conclusions According to this study, both probes are reliable and safe for neural mapping. The kind of probe used during neural monitoring is based on surgical situations and surgeon preference. Level of Evidence Level 3 (According to Oxford Centre for Evidence-Based Medicine 2011 Levels of Evidence) Laryngoscope, 2021, Ege University Scientific Research Projects Commission, This study was funded by Ege University Scientific Research Projects Commission.

Background Care for patients with thyroid nodules is complex and multidisciplinary, and research demonstrates variation in care. The objective was to develop clinical guidelines and quality metrics to reduce unwarranted variation and improve quality. Methods Multidisciplinary expert consensus and modified Delphi approach. Source documents were workflow algorithms from Kaiser Permanente Northern California and Cancer Care of Ontario based on the 2015 American Thyroid Association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer. Results A consensus-based, unified preoperative, perioperative, and postoperative workflow was developed for North American use. Twenty-one panelists achieved consensus on 16 statements about workflow-embedded process and outcomes metrics addressing safety, access, appropriateness, efficiency, effectiveness, and patient centeredness of care. Conclusion A panel of Canadian and United States experts achieved consensus on workflows and quality metric statements to help reduce unwarranted variation in care, improving overall quality of care for patients diagnosed with thyroid nodules.

Objectives/hypothesis Intraoperative neural monitoring is a useful adjunct for the laryngeal nerve function assessment during thyroid and parathyroid surgery. Typically, monitoring is performed by measurement of electromyographic responses recorded by endotracheal tube (ETT) surface electrodes. Tube position alterations during surgery can cause displacement of the electrodes relative to the vocal cords, leading to false positive loss of signal. Numerous reports have denoted monitoring equipment-related issues, especially endotracheal tube displacement, as the dominant source of false positive error. The false positive error may result in inappropriate decisions by the surgeon. This study tests the hypothesis that anterior laryngeal electrodes (ALEs) can help reduce this error. Placement of ALEs directly onto the thyroid cartilage represent an adjunctive and possible alternative method to standard ETT surface electrodes. Study design Retrospective review. Methods Fifteen consecutive patients undergoing thyroid and parathyroid surgery with intraoperative neuromonitoring using both ETT electrodes and ALEs were studied. Data collected included site of neural stimulation, laterality, and electromyographic parameters. Results With vagal and recurrent laryngeal nerve stimulation, the ALEs recorded mean vocalis muscle waveform amplitude within 83% of that recorded with standard ETT electrodes. The latency measurements with the anterior laryngeal and endotracheal electrodes were similar, with both electrodes recording significantly longer latency for the left vagus nerve as compared to the right vagus nerve. With superior laryngeal nerve stimulation, the ALEs recorded a 800% greater mean amplitude than the ETT electrodes. The ALEs demonstrated similar sensitivity to stimulation at low current as ETT electrodes and provided stable intraoperative monitoring information. Conclusions Compared to ETT surface electrodes, the ALEs provide similar and stable electromyographic responses with equal sensitivity for recording evoked responses during neural monitoring in thyroid and parathyroid surgery. The ALEs offer significantly more robust monitoring of the external branch of the superior laryngeal nerve. Furthermore, ALEs are contained within the operative field, are totally surgeon controlled, and are unaffected by the potential vicissitudes of ETT position during surgery. Level of evidence 4 Laryngoscope, 128:2910-2915, 2018.

This publication offers modern, state-of-the-art International Neural Monitoring Study Group (INMSG) guidelines based on a detailed review of the recent monitoring literature. The guidelines outline evidence-based definitions of adverse electrophysiologic events, especially loss of signal, and their incorporation in surgical strategy. These recommendations are designed to reduce technique variations, enhance the quality of neural monitoring, and assist surgeons in the clinical decision-making process involved in surgical management of recurrent laryngeal nerve. The guidelines are published in conjunction with the INMSG Guidelines Part II, Optimal Recurrent Laryngeal Nerve Management for Invasive Thyroid Cancer-Incorporation of Surgical, Laryngeal, and Neural Electrophysiologic Data. Laryngoscope, 128:S1-S17, 2018.

The purpose of this publication was to inform surgeons as to the modern state-of-the-art evidence-based guidelines for management of the recurrent laryngeal nerve invaded by malignancy through blending the domains of 1) surgical intraoperative information, 2) preoperative glottic function, and 3) intraoperative real-time electrophysiologic information. These guidelines generated by the International Neural Monitoring Study Group (INMSG) are envisioned to assist the clinical decision-making process involved in recurrent laryngeal nerve management during thyroid surgery by incorporating the important information domains of not only gross surgical findings but also intraoperative recurrent laryngeal nerve functional status and preoperative laryngoscopy findings. These guidelines are presented mainly through algorithmic workflow diagrams for convenience and the ease of application. These guidelines are published in conjunction with the INMSG Guidelines Part I: Staging Bilateral Thyroid Surgery With Monitoring Loss of Signal. Level of Evidence: 5 Laryngoscope, 128:S18-S27, 2018.

Decisions about resource allocation are increasingly based on value trade-offs between health outcomes and cost. This process relies on comprehensive and standardized definitions of health status that accurately measure the physical, mental, and social well-being of patients across disease states. These metrics, assessed through clinical trials, observational studies, and health surveys, can facilitate the integration of patient preferences into clinical practice. This ninth installment in the Evidence-Based Medicine in Otolaryngology Series is a practical overview of health outcome valuation, as well as the integration of both quality and quantity of life into standardized metrics for health research, program planning, and resource allocation. Tools for measuring preference-based health states, measures of effectiveness, and the application of metrics in economic evaluations are discussed.

Objectives Deficits related to inadequate clinical communication can result in incorrect diagnoses, inappropriate surgery, incorrect disease stratification, pathologic reporting, and/or interpretation. There are currently no validated or defined solutions to disease-specific communication with regard to thyroid care. Methods We propose a solution that could ameliorate problems arising from inadequate disease-specific communications between physicians through the development of a thyroid disease-specific database, the Thyroid Care Collaborative. Results To improve the quality of thyroid nodule and cancer care, we have developed an imaging module for enhanced reporting of ultrasound, cytologic, surgical, and pathologic details that are obtained during the workup and treatment of a patient. Conclusion The main advantages of this disease-specific, dynamic, three-dimensional, anatomic disease map are: 1) portability across institutions and disciplines, 2) disease specificity to thyroid nodule and cancer care, and 3) ability to trigger more detailed evaluation or reconciliation of any change in a patient's status regarding the nature or the extent of a patient's disease. The first and second advantages above have been identified as areas representing opportunities for quality improvement in health informatics research. Laryngoscope, 129:269-274, 2019.

Background The increasing use of intraoperative neuromonitoring (IONM) in thyroid surgery has revealed the need to develop new strategies for cases in which a loss of signal (LOS) occurs on the first side of a planned total thyroidectomy. Objectives This study reviews the experience of the authors in using IONM for planned total thyroidectomy after LOS on the first thyroid lobe. The aims were to estimate the incidence of LOS on the first side of resection and to compare intraoperative strategies applied after this event. Materials and Methods Intermittent IONM was performed with stimulation of both the vagal nerve and the recurrent laryngeal nerve (RLN) (V1, R1, R2, V2). Patients underwent pre- and postoperative laryngoscopy. Before surgery, patients were informed that staged thyroidectomy might be required. Results This study analyzed 803 consecutive thyroid procedures. Of these, V2 LOS (

Objective Minimally invasive parathyroidectomy requires accurate preoperative localization techniques. There is considerable controversy about the effectiveness of selective parathyroid venous sampling (sPVS) in primary hyperparathyroidism (PHPT) patients. The aim of this meta-analysis is to examine the diagnostic accuracy of sPVS as a preoperative localization modality in PHPT. Methods Studies evaluating the diagnostic accuracy of sPVS for PHPT were electronically searched in the PubMed, EMBASE, Web of Science, and Cochrane Controlled Trials Register databases. Two independent authors reviewed the studies, and revised quality assessment of diagnostic accuracy study tool was used for the quality assessment. Study heterogeneity and pooled estimates were calculated. Results Two hundred and two unique studies were identified. Of those, 12 studies were included in the meta-analysis. Pooled sensitivity, specificity, and positive likelihood ratio (PLR) of sPVS were 74%, 41%, and 1.55, respectively. The area-under-the-receiver operating characteristic curve was 0.684, indicating an average discriminatory ability of sPVS. On comparison between sPVS and noninvasive imaging modalities, sensitivity, PLR, and positive posttest probability were significantly higher in sPVS compared to noninvasive imaging modalities. Interestingly, super-selective venous sampling had the highest sensitivity, accuracy, and positive posttest probability compared to other parathyroid venous sampling techniques. Conclusion This is the first meta-analysis to examine the accuracy of sPVS in PHPT. sPVS had higher pooled sensitivity when compared to noninvasive modalities in revision parathyroid surgery. However, the invasiveness of this technique does not favor its routine use for preoperative localization. Super-selective venous sampling was the most accurate among all other parathyroid venous sampling techniques. Laryngoscope, 2662-2667, 2018.

We investigated the effects of protein-protein interaction strength on interfacial viscoelastic properties and aggregation of recombinant human interleukin-1 receptor antagonist (rhIL-1ra) at silicone oil-water interfaces. Osmotic second virial coefficients determined by static light scattering were used to quantify protein-protein interactions in bulk solution. Attractive protein-protein interactions dominated at low ionic strengths and their magnitude decreased with increasing ionic strength, in contrast to repulsive interactions that would be expected based on uniformly charged sphere models. Interfacial shear rheometry was used to characterize rhIL-1ra interfacial layers. More attractive protein-protein interactions in bulk solution correlated with stronger interfacial gels. Thioflavin-T fluorescence measurements indicated that the intermolecular β-sheet content of rhIL-1ra incubated in the presence of silicone oil-water interfaces correlated with gel strength. Siliconized syringes were used to probe the effects of mechanical perturbation of the interfacial gel layers. When rhIL-1ra solutions in siliconized glass syringes were subjected to end-over-end rotation, monomeric rhIL-1ra was lost from solution, and particles containing aggregated protein were released into the bulk aqueous phase. The loss of monomeric rhIL-1ra in response to mechanical perturbation was highest under the conditions where the strongest gels were observed. Aggregation of rhIL-1ra was strictly interface-induced and growth of aggregates in the bulk solution was not observed, even in the presence of particles released from silicone oil-water interfaces.

Objectives/hypothesis Continuous intraoperative neuromonitoring (CIONM) of the vagus nerve was proposed to obtained frequent repetitive electromyography (EMG) data to recognize early change in intraoperative function of the recurrent laryngeal nerve. We examine our initial experience using this technology. Study design Retrospective review. Methods Data for all patients who underwent neck surgery by a single surgeon at a North American institution over a 5-year period were reviewed. CIONM was used in cases with possible higher risk of traction injury and according to surgeon preference. In these cases, stretch injury was established by warning alarm with threshold of ≥50% reduction in amplitude and/or ≥ 10% increase in latency. Preoperative and postoperative direct laryngoscopy was performed for all patients. Results A total of 879 endocrine neck surgeries were performed. CIONM was used to monitor 455 recurrent laryngeal nerves (RLNs) in 344 (39.1%) surgeries. An automatic periodic stimulation (APS) alarm detected impending nerve injury in 33 (9.6%) cases by 64.9% ± 12.7% decrease in amplitude and by 27.3% increase in latency in one case. A total loss of signal (LOS) was detected in 15 (4.36%) cases. The immediate release of causative retraction successfully preserved the nerves in all cases with impending injury; however, there was no improvement in the LOS cases. Other than the cases with LOS, postoperative laryngoscopy showed normal vocal cord function in all cases. Conclusions APS technology is safe, feasible, and helpful in approximately 10% of cases in our series, which developed nascent neurapraxia adverse EMG changes associated with intraoperative RLN stretch that could be reversed intraoperatively. Level of evidence 4. Laryngoscope, 128:2429-2432, 2018.

Shared decision making (SDM) is a collaborative process in which patients, families, and clinicians develop a mutually agreed upon treatment plan when more than one reasonable treatment option exists. This cooperative engagement fosters improvements in patient satisfaction, disease management, and outcomes and also has the capacity to promote evidence-based care. Thus, this seventh installment of our Evidence-Based Medicine in Otolaryngology series focuses on SDM. We introduce SDM, including its potential to reduce decisional conflict and decisional regret, when it should be used, its potential benefits, barriers to implementation, and its role in the management of chronic disease and otolaryngological conditions.

Objectives During monitored thyroidectomy, displacement of the recurrent laryngeal nerve (RLN) or vagus nerve (VN) in some complicated cases can increase the risk of injury. Although increasing the stimulus current can facilitate nerve mapping and localization, the safety of a high-current stimulus remains unknown. Therefore, this study evaluated the safety of a high-current stimulus in a porcine model. Methods Short-duration (1 minute), high-current (3, 5, 10, 15, 20, 25, and 30 mA at 4Hz) stimulus pulses were repeatedly applied to the RLN or VN in six anesthetized piglets. The safety of the high-current stimulus pulses was assessed in terms of hemodynamic stability during VN stimulation and in terms of nerve function integrity after VN and RLN stimulation. Results During VN stimulation with a high-current stimulus pulse, sinus rhythms in all six piglets showed stable heart rates, and mean arterial pressure was unaffected. High-current stimulation of the VN and the RLN did not affect electromyography amplitude or latency. Conclusion This porcine study showed that applying a short-duration, high-current stimulus pulse to the VN or RLN during monitored thyroidectomy has no harmful effects. In clinical practice, a short duration of high-current stimulus can be applied to facilitate neural mapping, especially in patients with disoriented nerve positions. Level of evidence NA. Laryngoscope, 128:2206-2212, 2018.

Background The primary purposes of this interdisciplinary consensus statement were to review the relevant indications for central neck dissection (CND) in patients with papillary thyroid cancer (PTC) and to outline the appropriate extent and relevant techniques required to accomplish a safe and effective CND. Methods A writing group convened by the American Head and Neck Society (AHNS) Endocrine Committee was tasked with identifying the important clinical elements to consider when managing the central neck compartment in patients with PTC based on available evidence in the literature, and the group's collective experience. The position statement paper was then submitted to the full Endocrine Committee, Education Committee, and AHNS Council. Results This consensus statement was developed to inform the clinical decision-making process when managing the central neck compartment in patients with PTC from the AHNS. This document is intended to provide clarity through definitions as well as a basic guideline from which to manage the central neck. It is our hope that this improves the quality and reduces variation in management of the central neck, facilitates communication, and furthers research for patients with thyroid cancer. Conclusion This represents, in our opinion, contemporary optimal surgical care for this patient population and is endorsed by the American Head and Neck Society. © 2017 Wiley Periodicals, Inc. Head Neck, 2017

Objective To characterize nodal disease of patients presenting with papillary thyroid carcinoma (PTC) Study Design Retrospective chart review. Methods PTC patients who underwent thyroidectomy and/or neck dissection (revision/primary) from 2004 to 2009 at a tertiary-care hospital were reviewed. Preoperative computed tomography (CT) scan and ultrasonography were utilized to identify macroscopic, clinically apparent nodal metastasis (cN+). Demographic data, type of surgery, nodal disease, and primary tumor information were recorded. Results Of 416 patients reviewed, 35% had cN+ on initial presentation (IP); of these, 88% and 50% had central (CND) and lateral nodal disease (LND), respectively. The presence of ectopic nodal (END) metastases (nodal disease outside typical CND or LND locations) was absent on IP but occurred in 9% of patients with nodal recurrence. END was typically found in the retropharyngeal area but also was noted in the sublingual region, subcutaneous location, axilla, and chest wall. Extrathyroidal extension (ETE) was found in 8.9% without nodal disease, 33.1% with nodal disease, and 57.1% with END (P < 0.0001). Primary tumor size greater than 4 cm (P = 0.05) was associated with nodal disease. Conclusion This report represents a large series describing characteristics of the primary PTC tumor and associated nodal disease not only in the central and lateral neck but also in the ectopic locations. Our results suggest that a significant proportion of patients will have nodal disease in the central compartment on IP, especially younger patients. ETE and tumor size are associated with macroscopic nodal disease (including END). Nine percent of the patients with nodal recurrence had ectopic nodes occurring in various locations, most commonly in the retropharynx. CT scan can assist with identification and surgical planning of recurrent nodal disease. Level of Evidence 4. Laryngoscope, 127:1959–1964, 2017