Overview of Thyroid and Parathyroid Disease: The Otolaryngology Perspective.

The management of thyroid and parathyroid pathology varies widely, with unifying goals of symptomatic control and mitigating patient morbidity. In general, surgery is indicated when addressing malignancy or when medical management is insufficient. Over the last few decades, treatment paradigms for patients with head and neck endocrine disease have shifted significantly as our understanding of disease processes has expanded and with the advent of numerous relevant technologies. Here we provide a general overview of thyroid and parathyroid disease that may be managed by the otolaryngologist, with attention to emerging strategies in diagnosis and treatment.

A multi-institutional study evaluating and describing atypical parathyroid tumors discovered after parathyroidectomy.

Objective: To describe common intraoperative and pathologic findings of atypical parathyroid tumors (APTs) and evaluate clinical outcomes in patients undergoing parathyroidectomy. Methods: In this multi-institutional retrospective case series, data were collected from patients who underwent parathyroidectomy from 2000 to 2018 from three tertiary care institutions. APTs were defined according to the AJCC eighth edition guidelines and retrospective chart review was performed to evaluate the incidence of recurrent laryngeal nerve injury, recurrence of disease, and disease-specific mortality. Results: Twenty-eight patients were identified with a histopathologic diagnosis of atypical tumor. Mean age was 56 years (range, 23-83) and 68% (19/28) were female. All patients had an initial diagnosis of primary hyperparathyroidism with 21% (6/28) exhibiting clinical loss of bone density and 32% (9/28) presenting with nephrolithiasis or renal dysfunction. Intraoperatively, 29% (8/28) required thyroid lobectomy, 29% (8/28) had gross adherence to adjacent structures and 46% (13/28) had RLN adherence. The most common pathologic finding was fibrosis 46% (13/28). Postoperative complications include RLN paresis/paralysis in 14% (4/28) and hungry bone syndrome in 7% (2/28). No patients with a diagnosis of atypical tumor developed recurrent disease, however there was one patient that had persistent disease and hypercalcemia that is being observed. There were 96% (27/28) patients alive at last follow-up, with one death unrelated to disease. Conclusion: Despite the new AJCC categorization of atypical tumors staged as Tis, we observed no recurrence of disease after resection and no disease-specific mortality. However, patients with atypical tumors may be at increased risk for recurrent laryngeal nerve injury and incomplete resection.

Surgery Is Underutilized in the Management of Tertiary Hyperparathyroidism.

INTRODUCTION: Tertiary hyperparathyroidism (3HPT) is observed in up to 40% of renal transplant patients. Standard guidelines defining 3HPT and indications for operative intervention are not well described. METHODS: We conducted a retrospective, single-institution cohort study of patients who underwent renal transplant between January 1, 2012 and January 30, 2018, with a minimum of 13-month follow-up and at least 1 y of allograft function. We defined 3HPT as having elevated serum level parathyroid hormone (>88 pg/mL) after successful renal transplantation or multiple instances of elevated serum calcium starting at least 3 mo after transplant. We compared graft failure rates after stratifying the cohort based on management strategy: expectant, medical management with cinacalcet, and parathyroidectomy. RESULTS: Out of the 381 transplanted patients with functional grafts at 1 y, 178 patients (46.6%) were found to have 3HPT. One hundred twenty-nine patients (72.5%) were managed expectantly without medications, 35 patients (19.7%) were managed medically, and 14 patients (7.8%) were managed with parathyroidectomy. Twenty-two patients (17.1%) in the observation group had graft failure, 4 patients (11.4%) in the medically managed group had graft failure, and 0 patients in the surgery group had graft failure. Surgical intervention was associated with decreased renal allograft failure when compared to the combined cohort of nonoperative 3HPT patients (P = 0.03). All patients who underwent parathyroidectomy were cured and did not have graft failure as of December 30, 2019. Calcium elevation, but not PTH elevation, was associated with referral for parathyroidectomy on multivariable logistic regression analysis (P < 0.01). CONCLUSIONS: At our institution, the referral rate for parathyroidectomy among patients with 3HPT remains low. Parathyroidectomy was associated with high cure rates and reduced graft failure. Surgery may be underutilized in the management of 3HPT.

Avoiding delays in time to renal transplantation: Pretransplant thyroid malignancy does not affect patient or graft survival after renal transplantation.

BACKGROUND: Pretransplant malignancy is associated with decreased patient and graft survival. Current US guidelines recommend a 2- to 5-year, tumor-free waiting period before transplantation. No large studies have examined the specific, modern day risk of pretransplant thyroid malignancy on patient and graft survival after renal transplant. METHODS: The United Network for Organ Sharing database was queried for all adult isolated renal transplant recipients between 2003 and 2019. Patient characteristics, rates of post-transplant malignancy, and survival were compared between patients with pretransplant thyroid malignancy and without pretransplant thyroid malignancy. RESULTS: Eighty-six patients had pretransplant thyroid malignancy diagnosed after listing and before renal transplantation. Both overall and graft survival were similar between cohorts (P > .05). There was no significant association between pretransplant thyroid malignancy and patient (hazard ratio: 0.66; P = .31) or graft (hazard ratio:0.32; P = .11) survival on multivariate analysis. Waitlist duration for pretransplant thyroid malignancy patients was significantly increased (1,444 vs 438 days; P < .01), which translated to increased dialysis duration (2,234 vs 1,201 days, P < .01). Pretransplant thyroid malignancy patients did not experience increased post-transplant malignancy (P = .21). CONCLUSION: Given no association with decreased patient or allograft survival, our findings suggest that pretransplant thyroid malignancy patients are unnecessarily subjected to increased wait-list duration before transplant. We recommend an individualized approach for pretransplant thyroid malignancy patients diagnosed before or after listing.

Critical Review and Consensus Statement for Neural Monitoring in Otolaryngologic Head, Neck, and Endocrine Surgery.

BACKGROUND: Enhancing patient outcomes in an array of surgical procedures in the head and neck requires the maintenance of complex regional functions through the protection of cranial nerve integrity. This review and consensus statement cover the scope of cranial nerve monitoring of all cranial nerves that are of practical importance in head, neck, and endocrine surgery except for cranial nerves VII and VIII within the temporal bone. Complete and applied understanding of neurophysiologic principles facilitates the surgeon's ability to monitor the at-risk nerve. METHODS: The American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) identified the need for a consensus statement on cranial nerve monitoring. An AAO-HNS task force was created through soliciting experts on the subject. Relevant domains were identified, including residency education, neurophysiology, application, and various techniques for monitoring pertinent cranial nerves. A document was generated to incorporate and consolidate these domains. The panel used a modified Delphi method for consensus generation. RESULTS: Consensus was achieved in the domains of education needs and anesthesia considerations, as well as setup, troubleshooting, and documentation. Specific cranial nerve monitoring was evaluated and reached consensus for all cranial nerves in statement 4 with the exception of the spinal accessory nerve. Although the spinal accessory nerve's value can never be marginalized, the task force did not feel that the existing literature was as robust to support a recommendation of routine monitoring of this nerve. In contrast, there is robust supporting literature cited and consensus for routine monitoring in certain procedures, such as thyroid surgery, to optimize patient outcomes. CONCLUSIONS: The AAO-HNS Cranial Nerve Monitoring Task Force has provided a state-of-the-art review in neural monitoring in otolaryngologic head, neck, and endocrine surgery. The evidence-based review was complemented by consensus statements utilizing a modified Delphi method to prioritize key statements to enhance patient outcomes in an array of surgical procedures in the head and neck. A precise definition of what actually constitutes intraoperative nerve monitoring and its benefits have been provided.

Thyroid nodules >4 cm with atypia of undetermined significance cytology independently associate with malignant pathology.

BACKGROUND: The risk of malignancy from nodules with atypia of undetermined significance cytology is estimated between 5% and 15%, though more recent studies suggest rates upwards of 48%. This study sought to characterize preoperative predictors of malignancy to aid in clinical decision-making. METHODS: We performed a single institution retrospective review of all adult patients with unilateral thyroid nodules demonstrating atypia of undetermined significance cytology between March 1, 2013 and June 1, 2019 who underwent surgical resection (n = 266). Univariate and multivariate logistical analysis was performed using clinical and demographic variables to identify potential preoperative characteristics associated with malignant disease. RESULTS: Malignancy was identified on final pathology in 24.7% of patients with atypia of undetermined significance cytology. Age, sex, exposure to ionizing radiation, family history of thyroid cancer, Hashimoto's disease, Afirma suspicious results, and smoking were not associated with malignancy on both univariate and multivariate analysis. Nodule size >4 cm was independently associated with malignancy risk on both univariate (odds ratio 2.44, 1.09-5.43, P < .03) and multivariate (odds ratio 2.96, 1.27-6.87, P < .02) analysis. CONCLUSION: The results of this study demonstrate that nodules with atypia of undetermined significance cytology >4 cm are strongly associated with malignancy. We recommend strong consideration of surgery for all patients with thyroid nodules >4 cm and atypia of undetermined significance cytology.

Radiofrequency ablation and related ultrasound-guided ablation technologies for treatment of benign and malignant thyroid disease: An international multidisciplinary consensus statement of the American Head and Neck Society Endocrine Surgery Section with the Asia Pacific Society of Thyroid Surgery, Associazione Medici Endocrinologi, British Association of Endocrine and Thyroid Surgeons, European Thyroid Association, Italian Society of Endocrine Surgery Units, Korean Society of Thyroid Radiology, Latin American Thyroid Society, and Thyroid Nodules Therapies Association.

BACKGROUND: The use of ultrasound-guided ablation procedures to treat both benign and malignant thyroid conditions is gaining increasing interest. This document has been developed as an international interdisciplinary evidence-based statement with a primary focus on radiofrequency ablation and is intended to serve as a manual for best practice application of ablation technologies. METHODS: A comprehensive literature review was conducted to guide statement development and generation of best practice recommendations. Modified Delphi method was applied to assess whether statements met consensus among the entire author panel. RESULTS: A review of the current state of ultrasound-guided ablation procedures for the treatment of benign and malignant thyroid conditions is presented. Eighteen best practice recommendations in topic areas of preprocedural evaluation, technique, postprocedural management, efficacy, potential complications, and implementation are provided. CONCLUSIONS: As ultrasound-guided ablation procedures are increasingly utilized in benign and malignant thyroid disease, evidence-based and thoughtful application of best practices is warranted.

Tribute to Dr. Takuo Aoyagi, inventor of pulse oximetry.

INTRODUCTION: Dr. Takuo Aoyagi invented pulse oximetry in 1974. Pulse oximeters are widely used worldwide, most recently making headlines during the COVID-19 pandemic. Dr. Aoyagi passed away on April 18, 2020, aware of the significance of his invention, but still actively searching for the theory that would take his invention to new heights. METHOD: Many people who knew Dr. Aoyagi, or knew of him and his invention, agreed to participate in this tribute to his work. The authors, from Japan and around the world, represent all aspects of the development of medical devices, including scientists and engineers, clinicians, academics, business people, and clinical practitioners. RESULTS: While the idea of pulse oximetry originated in Japan, device development lagged in Japan due to a lack of business, clinical, and academic interest. Awareness of the importance of anesthesia safety in the US, due to academic foresight and media attention, in combination with excellence in technological innovation, led to widespread use of pulse oximetry around the world. CONCLUSION: Dr. Aoyagi's final wish was to find a theory of pulse oximetry. We hope this tribute to him and his invention will inspire a new generation of scientists, clinicians, and related organizations to secure the foundation of the theory.

Do Ultrasound Patterns and Clinical Parameters Inform the Probability of Thyroid Cancer Predicted by Molecular Testing in Nodules with Indeterminate Cytology?

Background: Molecular testing (MT) is commonly used to refine cancer probability in thyroid nodules with indeterminate cytology. Whether or not ultrasound (US) patterns and clinical parameters can further inform the risk of thyroid cancer in nodules predicted to be positive or negative by MT remains unknown. The aim of this study was to test if clinical parameters, including patient age, sex, nodule size (by US), Bethesda category (III, IV, V), US pattern (American Thyroid Association [ATA] vs. American College of Radiology Thyroid Image Reporting and Data System [TI-RADS] systems), radiation exposure, or family history of thyroid cancer can modify the probability of thyroid cancer or noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) predicted by MT. Methods: We studied 257 thyroid nodules in 232 patients from 10 study centers with indeterminate fine needle aspiration cytology and informative MT results using the ThyroSeq v3 genomic classifier (TSv3). Univariate and multivariate logistic regression was used for data analysis. Results: The presence of cancer/NIFTP was associated with positive TSv3 results (odds ratio 61.39, p < 0.0001). On univariate regression, patient sex, age, and Bethesda category were associated with cancer/NIFTP probability (p < 0.05 for each). Although ATA (p = 0.1211) and TI-RADS (p = 0.1359) US categories demonstrated positive trends, neither was significantly associated with cancer/NIFTP probability. A multivariate regression model incorporating the four most informative non-MT covariates (sex, age, Bethesda category, and ATA US pattern; Model No. 1) yielded a C index of 0.653; R2 = 0.108. When TSv3 was added to Model number 1, the C index increased to 0.888; R2 = 0.572. However, age (p = 0.341), Bethesda category (p = 0.272), and ATA US pattern (p = 0.264) were nonsignificant, and other than TSv3 (p < 0.0001), male sex was the only non-MT parameter that potentially contributed to cancer/NIFTP risk (p = 0.095). The simplest and most efficient clinical model (No. 3) incorporated TSv3 and sex (C index = 0.889; R2 = 0.588). Conclusions: In this multicenter study of thyroid nodules with indeterminate cytology and MT, neither the ATA nor TI-RADS US scoring systems further informed the risk of cancer/NIFTP beyond that predicted by TSv3. Although age and Bethesda category were associated with cancer/NIFTP probability on univariate analysis, in sequential nomograms they provided limited incremental value above the high predictive ability of TSv3. Patient sex may contribute to cancer/NIFTP risk in thyroid nodules with indeterminate cytology.

Detection by real-time quaking-induced conversion (RT-QuIC), ELISA, and IHC of chronic wasting disease prion in lymph nodes from Pennsylvania white-tailed deer with specific PRNP genotypes.

Chronic wasting disease (CWD) is a prion-mediated, transmissible disease of cervids, including deer (Odocoileus spp.), which is characterized by spongiform encephalopathy and death of the prion-infected animals. Official surveillance in the United States using immunohistochemistry (IHC) and ELISA entails the laborious collection of lymphoid and/or brainstem tissue after death. New, highly sensitive prion detection methods, such as real-time quaking-induced conversion (RT-QuIC), have shown promise in detecting abnormal prions from both antemortem and postmortem specimens. We compared RT-QuIC with ELISA and IHC for CWD detection utilizing deer retropharyngeal lymph node (RLN) tissues in a diagnostic laboratory setting. The RLNs were collected postmortem from hunter-harvested animals. RT-QuIC showed 100% sensitivity and specificity for 50 deer RLN (35 positive by both IHC and ELISA, 15 negative) included in our study. All deer were also genotyped for PRNP polymorphism. Most deer were homozygous at codons 95, 96, 116, and 226 (QQ/GG/AA/QQ genotype, with frequency 0.86), which are the codons implicated in disease susceptibility. Heterozygosity was noticed in Pennsylvania deer, albeit at a very low frequency, for codons 95GS (0.06) and 96QH (0.08), but deer with these genotypes were still found to be CWD prion-infected.

Pathologic Features Associated With Molecular Subtypes of Well-Differentiated Thyroid Cancer.

OBJECTIVE: To determine the association between pathologic features and molecular classes (BRAF-like, RAS-like, and non-BRAF-like non-RAS-like [NBNR]). METHODS: Retrospective review of a merged database containing 676 patients, 84% (571/676) were assigned to a molecular class from publicly accessible sequenced data of thyroid neoplasms. RESULTS: The merged cohort included 571 neoplasms: 353 (62%) BRAF-like, 172 (30%) RAS-like, and 46 (8.1%) NBNR. Lymph node metastasis (any N1 disease) was present in 166/337 (49%) of BRAF-like, 23/164 (14%) of RAS-like, and 0/46 (0%) of NBNR and are significantly different (P < .001). Gross extra-thyroidal extension was observed in 27 patients, including 24/331 (7%) of BRAF-like, 2/160 (1%) of RAS-like, and 1/46 (2%) of NBNR (P = .01). N1B lymph node metastases or T4 disease was present in 74/333 (22%) of BRAF-like, 10/160 (6%) of RAS-like, and 1/46 (2%) of NBNR (P < .0001). Distant metastasis was present in 4/151 (2.6%) of BRAF-like, 2/50 (4%) of RAS-like and 0/46 for NBNR (P = .627). Angioinvasion was present in 0/81 (0%) of BRAF-like, 3/53 (6%) of RAS-like, and 3/46 (7%) of NBNR (P = .08); and multifocality was present in 27/81 (33%) of BRAF-like, 9/53 (17%) of RAS-like, and 1/46 (2%) for NBNR (P = .0001). CONCLUSION: Pathological features of metastasis, gross extra-thyroidal extension, and multifocality were more prevalent in BRAF-like samples compared to RAS-like and NBNR. A trend towards increased frequency of angioinvasion in RAS-like and NBNR cancers compared to BRAF-like samples was observed. Further studies are needed to evaluate if preoperative knowledge of molecular mutations in thyroid tumors aids in decision-making regarding extent of surgery.

Executive Summary of the American Association of Endocrine Surgeons Guidelines for the Definitive Surgical Management of Thyroid Disease in Adults.

OBJECTIVE: The aim of this study was to develop evidence-based recommendations for safe, effective and appropriate thyroidectomy. BACKGROUND: Surgical management of thyroid disease has evolved considerably over several decades leading to variability in rendered care. Over 100,000 thyroid operations are performed annually in the United States. METHODS: The medical literature from January 1, 1985 to November 9, 2018 was reviewed by a panel of 19 experts in thyroid disorders representing multiple disciplines. The authors used the best available evidence to construct surgical management recommendations. Levels of evidence were determined using the American College of Physicians grading system, and management recommendations were discussed to consensus. Members of the American Association of Endocrine Surgeons reviewed and commented on preliminary drafts of the content. RESULTS: These clinical guidelines analyze the indications for thyroidectomy as well as its definitions, technique, morbidity, and outcomes. Specific topics include Pathogenesis and Epidemiology, Initial Evaluation, Imaging, Fine Needle Aspiration Biopsy Diagnosis, Molecular Testing, Indications, Extent and Outcomes of Surgery, Preoperative Care, Initial Thyroidectomy, Perioperative Tissue Diagnosis, Nodal Dissection, Concurrent Parathyroidectomy, Hyperthyroid Conditions, Goiter, Adjuncts and Approaches Laryngology Familial Thyroid Cancer, Postoperative Care and Complications, Cancer Management, and Reoperation. CONCLUSION: Evidence-based guidelines were created to assist clinicians in the optimal surgical management of thyroid disease.

The American Association of Endocrine Surgeons Guidelines for the Definitive Surgical Management of Thyroid Disease in Adults.

OBJECTIVE: To develop evidence-based recommendations for safe, effective, and appropriate thyroidectomy. BACKGROUND: Surgical management of thyroid disease has evolved considerably over several decades leading to variability in rendered care. Over 100,000 thyroid operations are performed annually in the US. METHODS: The medical literature from 1/1/1985 to 11/9/2018 was reviewed by a panel of 19 experts in thyroid disorders representing multiple disciplines. The authors used the best available evidence to construct surgical management recommendations. Levels of evidence were determined using the American College of Physicians grading system, and management recommendations were discussed to consensus. Members of the American Association of Endocrine Surgeons reviewed and commented on preliminary drafts of the content. RESULTS: These clinical guidelines analyze the indications for thyroidectomy as well as its definitions, technique, morbidity, and outcomes. Specific topics include Pathogenesis and Epidemiology, Initial Evaluation, Imaging, Fine Needle Aspiration Biopsy Diagnosis, Molecular Testing, Indications, Extent and Outcomes of Surgery, Preoperative Care, Initial Thyroidectomy, Perioperative Tissue Diagnosis, Nodal Dissection, Concurrent Parathyroidectomy, Hyperthyroid Conditions, Goiter, Adjuncts and Approaches to Thyroidectomy, Laryngology, Familial Thyroid Cancer, Postoperative Care and Complications, Cancer Management, and Reoperation. CONCLUSIONS: Evidence-based guidelines were created to assist clinicians in the optimal surgical management of thyroid disease.

A Thyroid Genetic Classifier Correctly Predicts Benign Nodules with Indeterminate Cytology: Two Independent, Multicenter, Prospective Validation Trials.

Background: Although most thyroid nodules with indeterminate cytology are benign, in most of the world, surgery remains as the most frequent diagnostic approach. We have previously reported a 10-gene thyroid genetic classifier, which accurately predicts benign thyroid nodules. The assay is a prototype diagnostic kit suitable for reference laboratory testing and could potentially avoid unnecessary diagnostic surgery in patients with indeterminate thyroid cytology. Methods: Classifier performance was tested in two independent, ethnically diverse, prospective multicenter trials (TGCT-1/Chile and TGCT-2/USA). A total of 4061 fine-needle aspirations were collected from 15 institutions, of which 897 (22%) were called indeterminate. The clinical site was blind to the classifier score and the clinical laboratory blind to the pathology report. A matched surgical pathology and valid classifier score was available for 270 samples. Results: Cohorts showed significant differences, including (i) clinical site patient source (academic, 43% and 97% for TGCT-1 and -2, respectively); (ii) ethnic diversity, with a greater proportion of the Hispanic population (40% vs. 3%) for TGCT-1 and a greater proportion of African American (11% vs. 0%) and Asian (10% vs. 1%) populations for TGCT-2; and (iii) tumor size (mean of 1.7 and 2.5 cm for TGCT-1 and -2, respectively). Overall, there were no differences in the histopathological profile between cohorts. Forty-one of 155 and 45 of 115 nodules were malignant (cancer prevalence of 26% and 39% for TGCT-1 and -2, respectively). The classifier predicted 37 of 41 and 41 of 45 malignant nodules, yielding a sensitivity of 90% [95% confidence interval; CI 77-97] and 91% [95% CI 79-98] for TGCT-1 and -2, respectively. One hundred one of 114 and 61 of 70 nodules were correctly predicted as benign, yielding a specificity of 89% [95% CI 82-94] and 87% [95% CI 77-94], respectively. The negative predictive values for TGCT-1 and TGCT-2 were 96% and 94%, respectively, whereas the positive predictive values were 74% and 82%, respectively. The overall accuracy for both cohorts was 89%. Conclusions: Clinical validation of the classifier demonstrates equivalent performance in two independent and ethnically diverse cohorts, accurately predicting benign thyroid nodules that can undergo surveillance as an alternative to diagnostic surgery.

American Head and Neck Society Endocrine Surgery Section update on parathyroid imaging for surgical candidates with primary hyperparathyroidism.

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.

Clinical use of the STOP-BANG questionnaire to determine postoperative risk in veterans.

OBJECTIVES: To determine whether STOP-BANG (snoring, tiredness, observed apnea, high blood pressure, body mass index, age, neck circumference, gender) scores are associated with immediate postoperative adverse events in veterans undergoing surgery. METHODS: In this prospective cohort study, veterans presenting to the presurgical clinic at a Veterans Affairs hospital answered the STOP-BANG questionnaire, which was scored as high risk (5-8), intermediate risk (3-4), and low risk (0-2) for obstructive sleep apnea (OSA), during a 6-month study period. Immediate postoperative respiratory and cardiovascular adverse events were recorded. RESULTS: The patient population included 1,080 veterans. Ninety-five patients (8.8%) experienced adverse events, of which 74 (6.9%) were respiratory and 21 (1.9%) were cardiovascular in nature. Patients with high-risk STOP-BANG scores (5-8) had significantly greater odds of having an adverse event odds ratio (OR) 2.1 (95% confidence interval [CI]: 1.4, 3.3) and hypoxia OR 2.8 (95% CI: 1.7, 4.6) compared to those with low- to intermediate-risk scores (0-4). Among patients with OSA, those with high-risk scores (5-8) had greater odds of an adverse event OR 3.9 (95% CI: 1.1, 13.9) and hypoxia OR 3.7 (95% CI: 1.1, 13.0) compared to those with low- to intermediate-risk scores (0-4). Patients without a history of OSA with high-risk scores (5-8) did not have significantly greater odds of an adverse event OR 1.5 (95% CI: 0.82, 2.6) or a hypoxic event OR 1.7 (95% CI: 0.87, 3.4) compared to those with low- to intermediate-risk scores (0-4). CONCLUSION: The STOP-BANG questionnaire was useful in the veteran population because high-risk scores were predictive of adverse events, in particular, hypoxia for patients with a previous diagnosis of OSA. In the future, this may direct studies and clinical activities aimed at optimizing safe and effective perioperative practices. LEVEL OF EVIDENCE: 2b Laryngoscope, 129:259-264, 2019.

Performance of a Multigene Genomic Classifier in Thyroid Nodules With Indeterminate Cytology: A Prospective Blinded Multicenter Study.

Importance: Approximately 20% of fine-needle aspirations (FNA) of thyroid nodules have indeterminate cytology, most frequently Bethesda category III or IV. Diagnostic surgeries can be avoided for these patients if the nodules are reliably diagnosed as benign without surgery. Objective: To determine the diagnostic accuracy of a multigene classifier (GC) test (ThyroSeq v3) for cytologically indeterminate thyroid nodules. Design, Setting, and Participants: Prospective, blinded cohort study conducted at 10 medical centers, with 782 patients with 1013 nodules enrolled. Eligibility criteria were met in 256 patients with 286 nodules; central pathology review was performed on 274 nodules. Interventions: A total of 286 FNA samples from thyroid nodules underwent molecular analysis using the multigene GC (ThyroSeq v3). Main Outcomes and Measures: The primary outcome was diagnostic accuracy of the test for thyroid nodules with Bethesda III and IV cytology. The secondary outcome was prediction of cancer by specific genetic alterations in Bethesda III to V nodules. Results: Of the 286 cytologically indeterminate nodules, 206 (72%) were benign, 69 (24%) malignant, and 11 (4%) noninvasive follicular thyroid neoplasms with papillary-like nuclei (NIFTP). A total of 257 (90%) nodules (154 Bethesda III, 93 Bethesda IV, and 10 Bethesda V) had informative GC analysis, with 61% classified as negative and 39% as positive. In Bethesda III and IV nodules combined, the test demonstrated a 94% (95% CI, 86%-98%) sensitivity and 82% (95% CI, 75%-87%) specificity. With a cancer/NIFTP prevalence of 28%, the negative predictive value (NPV) was 97% (95% CI, 93%-99%) and the positive predictive value (PPV) was 66% (95% CI, 56%-75%). The observed 3% false-negative rate was similar to that of benign cytology, and the missed cancers were all low-risk tumors. Among nodules testing positive, specific groups of genetic alterations had cancer probabilities varying from 59% to 100%. Conclusions and Relevance: In this prospective, blinded, multicenter study, the multigene GC test demonstrated a high sensitivity/NPV and reasonably high specificity/PPV, which may obviate diagnostic surgery in up to 61% of patients with Bethesda III to IV indeterminate nodules, and up to 82% of all benign nodules with indeterminate cytology. Information on specific genetic alterations obtained from FNA may help inform individualized treatment of patients with a positive test result.

The Role of Community Health Needs Assessments in Medicalizing Poverty.

The Patient Protection and Affordable Care Act (ACA), passed in 2010, is considered by many to be the most significant healthcare overhaul since the 1960s, but part of its promise - improvement of population health through requirements for non-profit hospitals to provide "community benefit" - has not been met. This paper examines the history of community benefit legislation, how community benefit dollars are allocated, and innovative practices by a few hospitals and communities that are addressing primarily non-medical factors that influence health such as social disadvantage, attitudes, beliefs, risk exposure, and social inequalities.