Molecular Alterations and Comprehensive Clinical Management of Oncocytic Thyroid Carcinoma: A Review and Multidisciplinary 2023 Update.

Importance: Oncocytic (Hürthle cell) thyroid carcinoma is a follicular cell-derived neoplasm that accounts for approximately 5% of all thyroid cancers. Until recently, it was categorized as a follicular thyroid carcinoma, and its management was standardized with that of other differentiated thyroid carcinomas. In 2022, given an improved understanding of the unique molecular profile and clinical behavior of oncocytic thyroid carcinoma, the World Health Organization reclassified oncocytic thyroid carcinoma as distinct from follicular thyroid carcinoma. The International Thyroid Oncology Group and the American Head and Neck Society then collaborated to review the existing evidence on oncocytic thyroid carcinoma, from diagnosis through clinical management and follow-up surveillance. Observations: Given that oncocytic thyroid carcinoma was previously classified as a subtype of follicular thyroid carcinoma, it was clinically studied in that context. However, due to its low prevalence and previous classification schema, there are few studies that have specifically evaluated oncocytic thyroid carcinoma. Recent data indicate that oncocytic thyroid carcinoma is a distinct class of malignant thyroid tumor with a group of distinct genetic alterations and clinicopathologic features. Oncocytic thyroid carcinoma displays higher rates of somatic gene variants and genomic chromosomal loss of heterozygosity than do other thyroid cancers, and it harbors unique mitochondrial DNA variations. Clinically, oncocytic thyroid carcinoma is more likely to have locoregional (lymph node) metastases than is follicular thyroid carcinoma-with which it was formerly classified-and it develops distant metastases more frequently than papillary thyroid carcinoma. In addition, oncocytic thyroid carcinoma rarely absorbs radioiodine. Conclusions and Relevance: The findings of this review suggest that the distinct clinical presentation of oncocytic thyroid carcinoma, including its metastatic behavior and its reduced avidity to radioiodine therapy, warrants a tailored disease management approach. The reclassification of oncocytic thyroid carcinoma by the World Health Organization is an important milestone toward developing a specific and comprehensive clinical management for oncocytic thyroid carcinoma that considers its distinct characteristics.

Intraoperative Parathyroid Hormone Monitoring In Normohormonal Primary Hyperparathyroidism: How Low Do You Go?

OBJECTIVE: The primary goal of this study was to determine in patients with normohormonal primary hyperparathyroidism (NHHPT) what percent reduction in post-excision intraoperative parathyroid hormone (IOPTH) from baseline would yield a rate of cure comparable to that in patients with classical primary hyperparathyroidism (PHPT). METHODS: This is a retrospective cohort study of patients who underwent parathyroidectomy between July 2013 and February 2020. Demographic data, preoperative, intraoperative, and postoperative metrics were collected. Patients with NHHPT were compared to those with classical PHPT. Subgroup analyses were performed. RESULTS: Of the 496 patients included in the study, 66 (13.3%) were of the normohormonal variant based on preoperative intact parathyroid hormone (PTH) levels and 28 (5.6%) based on baseline IOPTH levels. The cure rates in the two normohormonal groups were not significantly different from their classical counterparts (98.4% and 100.0% vs. 97.1%, p = 1.000). The median percent decline in post-excision IOPTH from baseline that achieved cure in the normohormonal groups were 82.6% and 80.4% compared to their respective controls at 87.3%, p = 0.011 and p = 0.001. Although the rate of multiglandular disease was higher in one of the normohormonal variant groups, this difference was due to a higher rate of double adenomas, not four-gland hyperplasia. CONCLUSION: Patients with NHHPT undergoing parathyroidectomy can expect cure rates similar to that in patients with classical PHPT. The results of this study indicate that achieving an 80% drop or more in IOPTH levels predicts a high likelihood of cure. This is true irrespective of whether the patient is deemed normohormonal based on preoperative or intraoperative testing. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:2480-2484, 2024.

Emerging Imaging Technologies for Parathyroid Gland Identification and Vascular Assessment in Thyroid Surgery: A Review From the American Head and Neck Society Endocrine Surgery Section.

Importance: Identification and preservation of parathyroid glands (PGs) remain challenging despite advances in surgical techniques. Considerable morbidity and even mortality result from hypoparathyroidism caused by devascularization or inadvertent removal of PGs. Emerging imaging technologies hold promise to improve identification and preservation of PGs during thyroid surgery. Observation: This narrative review (1) comprehensively reviews PG identification and vascular assessment using near-infrared autofluorescence (NIRAF)-both label free and in combination with indocyanine green-based on a comprehensive literature review and (2) offers a manual for possible implementation these emerging technologies in thyroid surgery. Conclusions and Relevance: Emerging technologies hold promise to improve PG identification and preservation during thyroidectomy. Future research should address variables affecting the degree of fluorescence in NIRAF, standardization of signal quantification, definitions and standardization of parameters of indocyanine green injection that correlate with postoperative PG function, the financial effect of these emerging technologies on near-term and longer-term costs, the adoption learning curve and effect on surgical training, and long-term outcomes of key quality metrics in adequately powered randomized clinical trials evaluating PG preservation.

Human-nature connectedness as a pathway to sustainability: A global meta-analysis.

Internationally agreed sustainability goals are being missed. Here, we conduct global meta-analyses to assess how the extent to which humans see themselves as part of nature-known as human-nature connectedness (HNC)-can be used as a leverage point to reach sustainability. A meta-analysis of 147 correlational studies shows that individuals with high HNC had more pronature behaviours and were significantly healthier than those with low HNC. A meta-analysis of 59 experimental studies shows significant increases in HNC after manipulations involving contact with nature and mindfulness practices. Surprisingly, this same meta-analysis finds no significant effect of environmental education on HNC. Thus, HNC is positively linked to mind-sets that value sustainability and behaviours that enhance it. Further, we argue that HNC can be enhanced by targeted practices, and we identify those most likely to succeed. Our results suggest that enhancing HNC, via promotion of targeted practices, can improve sustainability and should be integrated into conservation policy.

A Genome for Edith's Checkerspot Butterfly: An Insect with Complex Host-Adaptive Suites and Rapid Evolutionary Responses to Environmental Changes.

Insects have been key players in the assessments of biodiversity impacts of anthropogenically driven environmental change, including the evolutionary and ecological impacts of climate change. Populations of Edith's Checkerspot Butterfly (Euphydryas editha) adapt rapidly to diverse environmental conditions, with numerous high-impact studies documenting these dynamics over several decades. However, studies of the underlying genetic bases of these responses have been hampered by missing genomic resources, limiting the ability to connect genomic responses to environmental change. Using a combination of Oxford Nanopore long reads, haplotype merging, HiC scaffolding followed by Illumina polishing, we generated a highly contiguous and complete assembly (contigs n = 142, N50 = 21.2 Mb, total length = 607.8 Mb; BUSCOs n = 5,286, single copy complete = 97.8%, duplicated = 0.9%, fragmented = 0.3%, missing = 1.0%). A total of 98% of the assembled genome was placed into 31 chromosomes, which displayed large-scale synteny with other well-characterized lepidopteran genomes. The E. editha genome, annotation, and functional descriptions now fill a missing gap for one of the leading field-based ecological model systems in North America.

The importance of eco-evolutionary dynamics for predicting and managing insect range shifts.

Evolutionary change impacts the rate at which insect pests, pollinators, or disease vectors expand or contract their geographic ranges. Although evolutionary changes, and their ecological feedbacks, strongly affect these risks and associated ecological and economic consequences, they are often underappreciated in management efforts. Greater rigor and scope in study design, coupled with innovative technologies and approaches, facilitates our understanding of the causes and consequences of eco-evolutionary dynamics in insect range shifts. Future efforts need to ensure that forecasts allow for demographic and evolutionary change and that management strategies will maximize (or minimize) the adaptive potential of range-shifting insects, with benefits for biodiversity and ecosystem services.

Pediatric intraoperative nerve monitoring during thyroid surgery: A review from the American Head and Neck Society Endocrine Surgery Section and the International Neural Monitoring Study Group.

Children are more likely to experience recurrent laryngeal nerve (RLN) injury during thyroid surgery. Intraoperative nerve monitoring (IONM) may assist in nerve identification and surgical decision making. A literature review of pediatric IONM was performed and used to inform a monitoring technique guide and expert opinion statements. Pediatric IONM is achieved using a variety of methods. When age-appropriate endotracheal tubes with integrated surface electrodes are not available, an alternative method should be used. Patient age and surgeon experience with laryngoscopy influence technique selection; four techniques are described in detail. Surgeons must be familiar with the nuances of monitoring technique and interpretation; opinion statements address optimizing this technology in children. Adult IONM guidelines may offer strategies for surgical decision making in children. In some cases, delay of second-sided surgery may reduce bilateral RLN injury risk.

Mosaics of climatic stress across species' ranges: tradeoffs cause adaptive evolution to limits of climatic tolerance.

Studies in birds and trees show climatic stresses distributed across species' ranges, not only at range limits. Here, new analyses from the butterfly Euphydryas editha reveal mechanisms generating these stresses: geographic mosaics of natural selection, acting on tradeoffs between climate adaptation and fitness traits, cause some range-central populations to evolve to limits of climatic tolerance, while others remain resilient. In one ecotype, selection for predator avoidance drives evolution to limits of thermal tolerance. In a second ecotype, the endangered Bay Checkerspot, selection on fecundity drives evolution to the climate-sensitive limit of ability to complete development within the lifespans of ephemeral hosts, causing routinely high mortality from insect-host phenological asynchrony. The tradeoff between maternal fecundity and offspring mortality generated similar values of fitness on different dates, partly explaining why fecundity varied by more than an order of magnitude. Evolutionary response to the tradeoff rendered climatic variability the main driver of Bay Checkerspot dynamics, and increases in this variability, associated with climate change, were a key factor behind permanent extinction of a protected metapopulation. Finally, we discuss implications for conservation planning of our finding that adaptive evolution can reduce population-level resilience to climate change and generate geographic mosaics of climatic stress. This article is part of the theme issue 'Species' ranges in the face of changing environments (Part II)'.

A better index for analysis of co-occurrence and similarity.

Scientists often need to know whether pairs of entities tend to occur together or independently. Standard approaches to this issue use co-occurrence indices such as Jaccard, Sørensen-Dice, and Simpson. We show that these indices are sensitive to the prevalences of the entities they describe and that this invalidates their interpretability. We propose an index, α, that is insensitive to prevalences. Published datasets reanalyzed with both α and Jaccard's index (J) yield profoundly different biological inferences. For example, a published analysis using J contradicted predictions of the island biogeography theory finding that community stability increased with increasing physical isolation. Reanalysis of the same dataset with the estimator [Formula: see text] reversed that result and supported theoretical predictions. We found similarly marked effects in reanalyses of antibiotic cross-resistance and human disease biomarkers. Our index α is not merely an improvement; its use changes data interpretation in fundamental ways.

Intraoperative Nerve Monitoring in Thyroidectomies for Malignancy: Does It Matter?

BACKGROUND: Recurrent laryngeal nerve (RLN) injury and postoperative hypocalcemia are potential complications of thyroidectomy, particularly in malignancy. Intraoperative nerve monitoring (IONM) remains controversial. We sought to evaluate the impact of IONM on these complications using a national data set. METHODS: The American College of Surgeons National Surgical Quality Improvement Program thyroidectomy-targeted data set was queried for patients who underwent thyroidectomies from 2016 to 2017. Patients were grouped according to IONM use. Logistic regression models were constructed to evaluate associations of variables with 30-day hypocalcemic events (HCEs) and RLN injury. Associations were expressed as odds ratios (ORs) with 95% confidence intervals (95% CIs). A subgroup analysis was performed of patients with malignancy. RESULTS: A total of 9527 patients were identified; 5969 (62.7%) underwent thyroidectomy with IONM and 3558 (37.3%) without. By multivariable analysis, IONM had protective associations with HCE (OR = .81, 95% CI = .68-.96; P = .013) and RLN injury (OR = .83, 95% CI = .69-.98; P = .033). Malignancy increased risk of HCE (OR = 1.21, 95% CI=1.01-1.45; P = .038) and RLN injury (OR = 1.22, 95% CI = 1.02-1.46; P = .034). A large proportion (5943/9527, 62.4%) of patients had malignancy; 3646 (61.3%) underwent thyroidectomy with IONM and 2297 (38.7%) without. In the subgroup analysis, IONM had stronger protective associations with HCE (OR = .73, 95% CI = .60-.90; P = .003) and RLN injury (OR = .76, 95% CI = .62-.94; P = .012). DISCUSSION: Malignancy was associated with increased risk of HCE and RLN injury. Intraoperative nerve monitoring had a protective association with HCE and RLN injury, both overall, and in the malignant subgroup. Intraoperative nerve monitoring was correlated with improved thyroidectomy outcomes, especially if the indication was malignancy. This warrants further study to clarify cause and effect.

Parathyroid Gland Autofluorescence Characteristics in Patients With Primary Hyperparathyroidism.

OBJECTIVE: Near-infrared imaging for intraoperative parathyroid gland (PG) detection has recently commanded significant attention. The PTeye (Medtronic, Minneapolis, MN) is a probe-based system for near-infrared autofluorescent evaluation of PGs. This study was designed to evaluate the capabilities of the PTeye in the setting of surgery for primary hyperparathyroidism. STUDY DESIGN: Prospective, Cohort study. METHODS: This single-institution, prospective cohort study included all patients undergoing parathyroidectomy for primary hyperparathyroidism with presumed single gland disease from June 2020 to December 2020. Absolute intensity and intensity ratios, with the thyroid as the control tissue, were obtained for the adenoma, ipsilateral normal PG, and adjacent tissue. The ability of the PTeye to function when not in direct contact with tissue was measured. RESULTS: Twenty-two patients were included. The median intensity ratio for the in situ adenomas was 4.38 (interquartile range [IQR]: 2.03-5.87), ipsilateral normal PGs 6.17 (IQR: 3.83-7.67), strap muscle 0.47 (IQR: 0.30-0.60), and fat 0.20 (IQR: 0.17-0.47). All normal PGs and 21/22 adenomas demonstrated autofluorescence above the detection threshold. The PTeye functioned at a maximum distance of separation of 10 mm through saline medium and 6 mm through clear solid medium. CONCLUSION: This study confirms the PTeye's ability to recognize PGs with a high degree of precision. The device was found to function properly even with the probe not in direct contact with the tissue. Although adenomatous PGs appear to demonstrate altered autofluorescent properties from normal PGs, additional research is required to determine if these differences are clinically useful. LEVEL OF EVIDENCE: 3 Laryngoscope, 132:715-721, 2022.

Hyperparathyroidism subsequent to radioactive iodine therapy for Graves' disease.

BACKGROUND: The development of primary hyperparathyroidism (PHPT) after radioactive iodine (RAI) treatment for thyroid disease is poorly characterized. The current study is the largest reported cohort and assesses the disease characteristics of patients treated for PHPT with a history of RAI exposure. METHODS: A retrospective analysis comparing patients, with and without a history of RAI treatment, who underwent surgery for PHPT. RESULTS: Twenty-eight of the 469 patients had a history of RAI treatment, all for Graves' disease. Patients with a history of RAI exposure had similar disease characteristics compared to control; however, patients with a history of RAI treatment had a higher rate of recurrence (7.4% vs 1.2%, p = 0.012). CONCLUSION: PHPT in patients with a history of RAI treatment can be approached in the same manner as RAI naive PHPT patients; however, the risk of recurrence of PHPT in RAI exposed patients may be higher.

Perioperative pain management and opioid-reduction in head and neck endocrine surgery: An American Head and Neck Society Endocrine Surgery Section consensus statement.

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.

Colonizations cause diversification of host preferences: A mechanism explaining increased generalization at range boundaries expanding under climate change.

As species' poleward range limits expand under climate change, generalists are expected to be better colonists than specialists, extending their ranges faster. This effect of specialization on range shifts has been shown, but so has the reverse cause-effect: in a global meta-analysis of butterfly diets, it was range expansions themselves that caused increases in population-level diet breadth. What could drive this unexpected process? We provide a novel behavioral mechanism by showing that, in a butterfly with extensive ecotypic variation, Edith's checkerspot, diet breadths increased after colonization events as diversification of individual host preferences pulled novel hosts into population diets. Subsequently, populations that persisted reverted toward monophagy. We draw together three lines of evidence from long-term studies of 15 independently evolving populations. First, direct observations showed a significant increase in specialization across decades: in recent censuses, eight populations used fewer host genera than in the 1980s while none used more. Second, behavioral preference-testing experiments showed that extinctions and recolonizations at two sites were followed, at first by diversification of heritable preference ranks and increases in diet breadth, and subsequently by homogenization of preferences and contractions of diet breadth. Third, we found a significant negative association in the 1980s between population-level diet breadth and genetic diversity. Populations with fewer mtDNA haplotypes had broader diets, extending to 3-4 host genera, while those with higher haplotype diversity were more specialized. We infer that diet breadth had increased in younger, recently colonized populations. Preference diversification after colonization events, whether caused by (cryptic) host shifts or by release of cryptic genetic variation after population bottlenecks, provides a mechanism for known effects of range shifts on diet specialization. Our results explain how colonizations at expanding range margins have increased population-level diet breadths, and predict that increasing specialization should accompany population persistence as current range edges become range interiors.

Preference Provides a Plethora of Problems (Don't Panic).

This review was solicited as an autobiography. The "problems" in my title have two meanings. First, they were professional difficulties caused by my decision to study oviposition preferences of butterflies that were not susceptible to traditional preference-testing designs. Until I provided video, my claim that the butterflies duplicate natural post-alighting host-assessment behavior when placed on hosts by hand was not credible, and the preference-testing technique that I had developed elicited skepticism, anger, and derision. The second meaning of "problems" is scientific. Insect preference comes with complex dimensionality that interacts with host acceptability. Part Two of this review describes how my group's work in this area has revealed unexpected axes of variation in plant-insect interactions-axes capable of frustrating attempts to derive unequivocal conclusions from apparently sensible experimental designs. The possibility that these complexities are lurking should be kept in mind as preference and performance experiments are devised.

Impact of a specialty trained billing team on an academic otolaryngology practice.

PURPOSE: To determine how the incorporation of specialty specific training for coders within a focused billing team affected revenue, efficiency, time to reimbursement, and physician satisfaction in an academic otolaryngology practice. MATERIALS AND METHODS: Our academic otolaryngology department recently implemented a new billing system, which incorporated additional training in otolaryngology surgical procedures for medical coders. A mixed model analysis of variance was used to compare billing outcomes for the 6 months before and 6 months after this new approach was initiated. The following metrics were analyzed: Current Procedural Terminology codes, total charges, time between services rendered and billing submission, and time to reimbursement. A survey of department physicians assessing satisfaction with the system was reviewed. RESULTS: There were 4087 Current Procedural Terminology codes included in the analysis. In comparing the periods before and after implementation of the new system, statistically significant decreases were found in the mean number of days to coding completion (19.3 to 12.0, respectively, p < 0.001), days to posting of charges (27.0 to 15.2, p < 0.001), days to final reimbursement (54.5 to 27.2, p < 0.001), and days to closure of form (179.2 to 76.6, p < 0.001). Physician satisfaction with communication and coder feedback increased from 36% to 64% after initiation of the new program. CONCLUSIONS: The implementation of additional specialty training for medical coders in the otolaryngology department of a large medical system was associated with improved revenue cycle efficiency. Additionally, this model appears to improve physician satisfaction and confidence with the coding system.

Salivary and lacrimal dysfunction after radioactive iodine for differentiated thyroid cancer: American Head and Neck Society Endocrine Surgery Section and Salivary Gland Section joint multidisciplinary clinical consensus statement of otolaryngology, ophthalmology, nuclear medicine and endocrinology.

BACKGROUND: Postoperative radioactive iodine (RAI) administration is widely utilized in patients with differentiated thyroid cancer. While beneficial in select patients, it is critical to recognize the potential negative sequelae of this treatment. The prevention, diagnosis, and management of the salivary and lacrimal complications of RAI exposure are addressed in this consensus statement. METHODS: A multidisciplinary panel of experts was convened under the auspices of the American Head and Neck Society Endocrine Surgery and Salivary Gland Sections. Following a comprehensive literature review to assess the current best evidence, this group developed six relevant consensus recommendations. RESULTS: Consensus recommendations on RAI were made in the areas of patient assessment, optimal utilization, complication prevention, and complication management. CONCLUSION: Salivary and lacrimal complications secondary to RAI exposure are common and need to be weighed when considering its use. The recommendations included in this statement provide direction for approaches to minimize and manage these complications.

Increased prevalence of neural monitoring during thyroidectomy: Global surgical survey.

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 < 0.001), with 70.4% of North American responders using it ubiquitously compared to 27.4% of non-North American responders. Preoperative laryngeal exam was performed more universally by North American surgeons and more selectively by non-North American surgeons (P < 0.001). Other attitudes toward their implementation and the postoperative laryngeal exam were similar. Surgeons ≤45 years of age and those with ≤15 years of practice used IONM more than their peers (P < 0.001). Thyroid surgery volume, fellowship training, and type of practice had no bearing on IONM use. CONCLUSION: The prevalence of IONM in thyroid and parathyroid surgeries has increased significantly over the past decade, with 83% of surgeons using IONM in some or all cases. Although IONM use may be more ubiquitous in North America, attitudes toward its implementation and pre- and postoperative laryngeal exams are fairly uniform. IONM use is more prevalent among younger surgeons, whereas its use has no correlation with thyroid surgery volume or type of practice. LEVEL OF EVIDENCE: 4 Laryngoscope, 130:1097-1104, 2020.