Obesity Promotes Marrow-Derived Myeloid Cell Accumulation while Exercise Reduces Proliferative Signaling in Colon Cancer.

PURPOSE: Obesity increases colon cancer risk that has been previously linked to marrow-derived myeloid cells. We previously demonstrated that exercise training (EX) prevents colon cancer initiation, potentially through reduced myelopoiesis. However, it remains unknown whether early myeloid cell accumulation and inflammation in the colon precedes carcinogenesis with high-fat diet (HFD)-induced obesity, and if EX can attenuate these effects. We hypothesized that obesity would promote colon carcinogenesis that was preceded by myeloid cell accumulation and inflammation that would be attenuated by EX. METHODS: C57BL/6 mice were randomized to a HFD or control (CON) diet for 8 weeks. The HFD mice switched to CON diet and all mice were given intraperitoneal injections of azoxymethane (AOM) to induce colon cancer and randomized into EX or sedentary (SED) conditions. RESULTS: HFD mice developed more aberrant crypt foci (ACF), a marker for early carcinogenesis, compared to CON (p < 0.01), and EX developed fewer ACF compared to SED (p < 0.0001). Marrow-derived (p < 0.001) CD206+ macrophages were elevated in HFD compared to CON at study week 16 (p < 0.01). Marrow-derived CD206- macrophages (p < 0.05) and marrow-derived (p < 0.05) CD206+ macrophages were more abundant in HFD compared to CON at study week 42. EX did not alter colon immune cell populations. ß-Catenin protein was higher in HFD compared to CON at study week 42 (p < 0.05), and STAT3 protein content was lower at study week 28 with EX compared to SED (p < 0.05). CONCLUSIONS: The results suggest that obesity promotes colon ACF formation, potentially through early inflammatory myeloid cell accumulation. Despite attenuating ACF, EX did not alter myeloid cell accumulation in the colon, suggesting that EX inhibits ACF formation through alternative mechanisms which may include reduced ß-Catenin and STAT3 signaling.

Comorbid Depression in Patients With Head and Neck Cancer Compared With Other Cancers.

Importance: Depression is more prevalent among individuals with cancer than in the general population and is correlated with increased mortality in patients with head and neck cancer (HNC) in particular. Objective: To compare the prevalence of depression between patients with HNC and patients with other cancers. Design, Setting, and Participants: This retrospective cohort study used population-level data on patients aged 18 years or older with cancer who participated in the 2019 National Health Interview Survey and had completed the Personal Health Questionnaire-8 (PHQ-8). The analysis was performed between August 7, 2023, and April 5, 2024. Exposure: Any cancer diagnosis. Main Outcomes and Measures: The main outcome was prevalence and severity of depression based on the PHQ-8. The magnitude of the difference in baseline characteristics was measured between patients with HNC and those with other cancer types, and 95% CIs were used to measure the precision of these estimates. Multivariable logistic regressions were used to evaluate the association of demographic, socioeconomic, anxiety, and clinical variables with depression. Results: From a weighted cohort of 23 496 725 adult patients with cancer, 377 080 were diagnosed with HNC (87.5% aged 51-84 years; 77.9% male). The prevalence of any depression on the PHQ-8 (mild, moderate, or severe) was 40.1% in patients with HNC vs 22.3% in patients with other cancers. Compared with patients with other cancers, patients with HNC were equally likely to screen positive for anxiety (23.6% vs 16.0%; difference, 7.6%; 95% CI, -5.9% to 21.1%), take medication for depression (10.1% vs 13.9%; difference, -3.8%; 95% CI, -11.9% to 4.4%), and state that they never feel depressed (59.7% vs 53.7%; difference, 6.0%; 95% CI, -9.1% to 21.0%). On multivariable logistic regression analysis, having HNC was associated with an increased likelihood of depression (odds ratio [OR], 2.94; 95% CI, 1.39-6.22). Other factors associated with depression were being unmarried or not living with a partner (OR, 1.94; 95% CI, 1.55-2.43) and having anxiety (OR, 23.14; 95% CI, 17.62-30.37). Conclusions and Relevance: This cohort study found that patients with HNC were twice as likely to screen positive for depression on a validated survey than those with other cancers, despite having similar rates of self-reported depression and depression medication use. These findings suggest that self-reporting of depression may result in underreporting and undertreatment in this population and, thus, a need for further work in developing interventions to improve identification of and optimize treatment for patients with HNC and comorbid depression.

Feasibility of a Novel 3D Ultrasound Imaging Technique for Intraoperative Margin Assessment during Tongue Cancer Surgery.

Squamous cell carcinoma (SCC) of the tongue is the most prevalent form of oral cavity cancer, with surgical intervention as the preferred method of treatment. Achieving negative or free resection margins of at least 5 mm is associated with improved local control and prolonged survival. Nonetheless, margins that are close (1-5 mm) or positive (less than 1 mm) are often observed in practice, especially for the deep margins. Ultrasound is a promising tool for assessing the depth of invasion, providing non-invasive, real-time imaging for accurate evaluation. We conducted a clinical trial using a novel portable 3D ultrasound imaging technique to assess ex vivo surgical margin assessment in the operating room. During the operation, resected surgical specimens underwent 3D ultrasound scanning. Four head and neck surgeons measured the surgical margins (deep, medial, and lateral) and tumor area on the 3D ultrasound volume. These results were then compared with the histopathology findings evaluated by two head and neck pathologists. Six patients diagnosed with tongue SCC (three T1 stage and three T2 stage) were enrolled for a consecutive cohort. The margin status was correctly categorized as free by 3D ultrasound in five cases, and one case with a "free" margin status was incorrectly categorized by 3D ultrasound as a "close" margin. The Pearson correlation between ultrasound and histopathology was 0.7 (p < 0.001), 0.6 (p < 0.001), and 0.3 (p < 0.05) for deep, medial, and lateral margin measurements, respectively. Bland-Altman analysis compared the mean difference and 95% limits of agreement (LOA) for deep margin measurement by 3D ultrasound and histopathology, with a mean difference of 0.7 mm (SD 1.15 mm). This clinical trial found that 3D ultrasound is accurate in deep margin measurements. The implementation of intraoperative 3D ultrasound imaging of surgical specimens may improve the number of free margins after tongue cancer treatment.

Parathyroid Adenoma Orientation for Gland Embryologic Origin on Ultrasonography.

Importance: Accurate preoperative localization is critical to success in targeted parathyroidectomy for primary hyperparathyroidism. Objective: To determine if the association between the long axis of a parathyroid adenoma (PTA) candidate and strap musculature on sagittal ultrasonography (US) can be used to predict the embryologic origin of the gland. Design, Setting, and Participants: This diagnostic study was performed using the Stanford Research Repository. Patients 18 years or older with primary hyperparathyroidism who underwent parathyroidectomy between January 2009 and October 2021 were considered. Additional inclusion criteria were having clear sagittal view of the adenoma candidate on US, confirmation of the gland of origin intraoperatively, and confirmation of hypercellular parathyroid on final pathology. Data were analyzed from October 2021 to June 2022. Exposures: B-mode US and surgical parathyroidectomy. Main Outcomes and Measures: The index test was using US to measure the angle between the long axis of an adenoma candidate and the strap musculature in the sagittal plane. This angle was used to test whether inferior and superior PTAs could be accurately assigned. The hypothesis was formulated prior to data collection. Results: A total of 426 patients (mean [range] age, 61.1 [20-96] years; 316 [74.2%] female) with 442 adenomas met inclusion criteria. Of the 442 adenomas, 314 (71.0%) had measurable angles, of which 204 (46.2%) were assigned a superior origin, 238 (53.8%) were assigned an inferior origin, and 128 (29%) were indeterminate. Of the surgically identified superior PTAs, 144 (70.6%) had a definable angle, and of the surgically identified inferior PTAs, 170 (71.4%) had a definable angle. The receiver operating characteristic analysis found 94° as the optimized angle for differentiating true negatives from true positives, with an overall sensitivity of 74% and specificity of 72%. This supported using 90° as a break point for US review. True positives were considered superior adenomas with an angle greater than 90°; true negatives were inferior adenomas with an angle less than 90°. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of angulation analysis for determining PTA origin were 72.2% (95% CI, 64.9%-79.5%), 73.5% (95% CI, 66.9%-80.1%), 69.8% (95% CI, 62.5%-77.1%), 75.8% (95% CI, 69.3%-82.3%), and 72.9%, respectively. A subgroup analysis of 426 adenomas using the posterior carotid artery border on transverse US as a surrogate for predicting gland origin showed the following for sensitivity, specificity, positive predictive value, negative predictive value, and accuracy: 49.5% (95% CI, 42.6%-56.4%), 82.3% (95% CI, 77.3%-87.3%), 71.4% (95% CI, 63.9%-78.9%), 64.6% (95% CI, 59.1%-70.1%), and 66.9%, respectively. Conclusions and Relevance: This diagnostic study showed that PTA angulation on sagittal plane US can be used to predict gland of origin and guide surgery. The relationship between adenoma and posterior carotid artery border on transverse US can also be used to predict gland origin. These easy-to-apply US-based tests can be used in conjunction with other imaging modalities to guide targeted parathyroidectomy.

Thyroid Nodule Rupture Following Radiofrequency Ablation for Benign Thyroid Nodules.

Importance: Nodule rupture is a rare but serious complication of thyroid radiofrequency ablation (RFA). With growing adoption of thyroid RFA across the US, an understanding of thyroid nodule rupture (TNR) is crucial for recognition, management, and, ultimately, prevention. Objective: To determine procedural and patient factors that may contribute to TNR and describe experiences in managing TNR while synthesizing existing literature. Design, Setting, and Participants: This retrospective case series examined all RFA procedures for benign thyroid nodules performed by 2 attending physicians at a single academic referral center between December 2019 and January 2024. A total of 298 consecutive patients underwent RFA for benign thyroid nodules. Criteria for offering RFA included nodules with 2 benign fine-needle aspirations, no suspicious ultrasonography features, a greatest dimension of 2 cm or greater, compressive or cosmetic concerns, and accessibility to a straight needle. Exposures: All RFAs were performed using ultrasonography guidance using the moving-shot technique and a 7-mm or 10-mm active tip. Main Outcomes and Measures: The primary outcome was TNR, and measures were procedure, nodule, and patient characteristics that may have contributed to its pathogenesis. Secondary outcomes were nodule volume reduction, thyroid function, and management and sequelae of TNR. The hypothesis on the pathogenesis of TNR was formed before data collection. Results: Six of 298 patients (2%; 4 women [67%]) with a mean age of 48.5 years (range, 34-65 years) experienced TNR for a mean of 36 days postprocedure (range, 19-54 days). The mean (SD) initial nodule volume among patients with TNR was 31.45 (16.52) mL, and 3 of 6 patients (50%) underwent prior lobectomy. All ruptures were anterior. All patients were treated conservatively, and none required surgery. Five patients recovered completely; the sixth and most recent patient was healing as of last follow-up. Conclusions and Relevance: There are limited data on the etiology and optimal management of TNR. These 6 cases of anterior rupture suggest that a potential contributor to TNR is thermal and mechanical trauma exerted at the fulcrum point during the moving-shot technique. The use of a smaller active tip (eg, 7 mm) and cessation of energy delivery before this point may help avoid TNR. More robust reporting of this complication may clarify risk factors for and enhance prevention of TNR.

Proposal for standardized ultrasound analysis of the salivary glands: Part 1 submandibular gland.

Objectives: The Salivary Gland Committee of the American Academy of Otolaryngology-Head and Neck Surgery seeks to standardize terminology and technique for ultrasonograpy used in the evaluation and treatment of salivary gland disorders. Methods: Development of expert opinion obtained through interaction with international practitioners representing multiple specialties. This committee work includes a comprehensive literature review with presentation of case examples to propose a standardized protocol for the language used in ultrasound salivary gland assessment. Results: A multiple segment proposal is initiated with this focus on the submandibular gland. We provide a concise rationale for recommended descriptive language highlighted by a more extensive supplement that includes an extensive literature review with additional case examples. Conclusion: Recommendations are provided to improve consistency both in performing and reporting submandibular gland ultrasound.

Redefining "Value" in Surgery: Development of a Comprehensive Value Score for Outpatient Endocrine Surgery.

OBJECTIVE: The value-based healthcare model aims to improve the quality of care and lower health care costs. The standard value equation (ie, Value = Quality/Cost), while conceptually useful, is grossly oversimplified and lacks clinical relevance. This study introduces a more detailed value equation that generates disease-specific value scores and incorporates real-world clinical and cost data to demonstrate its use. STUDY DESIGN: Prospective observational study. SETTING: Tertiary institution. METHODS: A comprehensive new health care value equation was developed that includes 23 unique inputs. Sixteen inputs represent quality (numerator) and 7 inputs represent cost (denominator). Patients undergoing thyroid or parathyroid surgery were enrolled, and data were entered into the new equation to generate surgery-specific value scores for each patient. A subanalysis was performed for telehealth visits. RESULTS: Ten patients were enrolled (60% female) with an average age of 62 years. The average total monetary cost per patient was $41,884 ($27,885 direct). Across all patients, the average total quality score was 0.99, and the cost score was 6.1, resulting in a final value score of 0.19. A subanalysis showed that changing a postoperative visit from in-person to telehealth would increase the value score by 0.66%. CONCLUSION: This analysis creates a comprehensive value equation for surgical services that incorporates the complexity of modern surgical care. The new equation includes objective and subjective outcomes and health equity, quantitatively compares the value of different surgical interventions and health care services, illustrates how specific interventions can lead to the higher value of care, and can serve as the framework for future value equations.

Radiofrequency ablation of benign thyroid nodules: A prospective, multi-institutional North American experience.

BACKGROUND: Radiofrequency ablation for benign thyroid nodules aims to achieve a volume reduction rate of ≥50%. However, factors that predict treatment success have not been defined in a large-scale study. METHODS: A prospective cohort study of biopsy-proven benign thyroid nodules treated with radiofrequency ablation at 3 institutions was performed. Patient demographics, nodule sonographic features, procedural data, and nodule volume reduction were evaluated. Binary logistic regression analysis was performed to identify features associated with treatment response. RESULTS: A total of 620 nodules were analyzed. The pooled median volume reduction rate at 12 months was 70.9% (interquartile range 52.9-86.6). At 1 year follow-up, 78.4% of nodules reached treatment success with a volume reduction rate ≥50%. The overall complication rate was 3.2% and included temporary voice changes (n = 14), vasovagal episodes (n = 5), nodule rupture (n = 3), and lightheadedness (n = 2). No permanent voice changes occurred. Four patients developed postprocedural hypothyroidism. Large baseline nodule volume (>20 mL) was associated with a lower rate of successful volume reduction (odds ratio 0.60 [0.37-0.976]). Large nodules achieved treatment success by 12-month follow-up at a rate of 64.5%, compared with 81.4% for small nodules and 87.2% for medium nodules. CONCLUSION: To our knowledge, this is the largest North American cohort of patients with benign thyroid nodules treated with radiofrequency ablation. Overall, radiofrequency ablation was an effective treatment option with a low risk of procedural complications. Large volume nodules (>20 mL) may be associated with a lower rate of successful reduction with radiofrequency ablation treatment.

Hyperthyroidism Due to Graves Disease After Radiofrequency Ablation.

Management options for benign, autonomously functioning, and malignant thyroid nodules were limited to surgery or targeting by radioactive iodine before the availability of radiofrequency ablation (RFA). Despite being a relatively new technique, RFA may be favored for patients of high surgical risk, and for those who wish to avoid hypothyroidism. Although insurance coverage for the procedure can be a significant barrier, several groups of investigators have shown improved quality of life for RFA compared to surgery, due to the less invasive nature and favorable risk profile. Hyperthyroidism due to transient thyroiditis is a known risk of RFA, secondary to direct trauma and subsequent thyroid hormone release. Here we present a case of an adult with large, symptomatic, multinodular goiter, with no prior history of thyroid autoimmunity, who underwent RFA with successful volume reduction of two nodules, but who developed acute hyperthyroidism due to Graves disease eight weeks after RFA. Larger studies evaluating the risks of RFA should evaluate for incident hyperthyroidism, specifically for Graves disease/thyroid autoimmunity, as this could represent an additional risk of the procedure.

International Expert Consensus on US Lexicon for Thyroid Nodules.

Multiple US-based systems for risk stratification of thyroid nodules are in use worldwide. Unfortunately, the malignancy probability assigned to a nodule varies, and terms and definitions are not consistent, leading to confusion and making it challenging to compare study results and craft revisions. Consistent application of these systems is further hampered by interobserver variability in identifying the sonographic features on which they are founded. In 2018, an international multidisciplinary group of 19 physicians with expertise in thyroid sonography (termed the International Thyroid Nodule Ultrasound Working Group) was convened with the goal of developing an international system, tentatively called the International Thyroid Imaging Reporting and Data System, or I-TIRADS, in two phases: (phase I) creation of a lexicon and atlas of US descriptors of thyroid nodules and (phase II) development of a system that estimates the malignancy risk of a thyroid nodule. This article presents the methods and results of phase I. The purpose herein is to show what has been accomplished thus far, as well as generate interest in and support for this effort in the global thyroid community.

History of Thyroid Surgery in the Last Century.

Before the 20th century, thyroid surgery was regarded as "horrid butchery" such that no honest and sensible surgeon would ever engage in it. Yet, by the mid-20th century, thyroidectomy had become a respected, life-saving, safe, and increasingly practiced operation. From Kocher to Wells and onward into the 21st century, the evolution of thyroid surgery has continued, enhanced by the integration of endocrinology, genetics, immunology, physiology, technology, training, and multidisciplinary care. The ability to personalize and optimize the care of thyroid disorders has been progressively achieved through shared insights and discoveries, highlights of which are described herein.

Opioid-Sparing Protocol for Endocrine Surgery (OSPREY): A Prospective Study.

BACKGROUND: Thyroid and parathyroid operations are among the most commonly performed surgeries in the world; however, there remains a paucity of prospective clinical trials evaluating the efficacy of opioid-sparing protocols after surgery. STUDY DESIGN: This prospective nonrandomized study was performed between March and October 2021. Participants self-selected their cohort of either an opioid-sparing protocol of acetaminophen/ibuprofen or a treatment-as-usual protocol with opioids. Primary endpoints were Overall Benefit of Analgesia Scores (OBAS) and opioid use as reported in daily medication logs. Data were recorded for 7 days. Multivariable regression, pooled variance t -tests, Mann-Whitney test, and chi-square tests were used to evaluate the results. RESULTS: A total of 87 participants were recruited; 48 participants opted for the opioid-sparing arm, and 39 participants opted for the treatment-as-usual arm. Patients in the opioid-sparing arm used significantly fewer opioids (morphine equivalents 0.77 ± 1.71 vs 3.34 ± 5.87, p = 0.042) but had no significant difference in OBAS (p = 0.37). Multivariable regression analysis demonstrated no significant difference in mean OBAS between treatment arms when controlling for age, sex, and type of surgery (p = 0.88). There were no major adverse events in either group. CONCLUSIONS: An opioid-sparing treatment algorithm based on the use of acetaminophen/ibuprofen may offer a safe and effective treatment algorithm compared to a primary opioid-focused treatment pathway. Randomized adequately powered studies are needed to confirm these findings.

Preoperative Evaluation of Thyroid Cancer: A Review of Current Best Practices.

OBJECTIVE: The incidence of thyroid cancer has significantly increased in recent decades. Although most thyroid cancers are small and carry an excellent prognosis, a subset of patients present with advanced thyroid cancer, which is associated with increased rates of morbidity and mortality. The management of thyroid cancer requires a thoughtful individualized approach to optimize oncologic outcomes and minimize morbidity associated with treatment. Because endocrinologists usually play a key role in the initial diagnosis and evaluation of thyroid cancers, a thorough understanding of the critical components of the preoperative evaluation facilitates the development of a timely and comprehensive management plan. The following review outlines considerations in the preoperative evaluation of patients with thyroid cancer. METHODS: A clinical review based on current literature was generated by a multidisciplinary author panel. RESULTS: A review of considerations in the preoperative evaluation of thyroid cancer is provided. The topic areas include initial clinical evaluation, imaging modalities, cytologic evaluation, and the evolving role of mutational testing. Special considerations in the management of advanced thyroid cancer are discussed. CONCLUSION: Thorough and thoughtful preoperative evaluation is critical for formulating an appropriate treatment strategy in the management of thyroid cancer.

Time-Driven Activity-Based Cost Comparison of Thyroid Lobectomy and Radiofrequency Ablation.

OBJECTIVE: Radiofrequency ablation (RFA) of benign thyroid nodules has gained traction for its therapeutic effectiveness, thyroid function preservation, and minimally invasive nature. While a growing body of evidence reports positive outcomes from thyroid RFA, financial comparisons between both procedures remain limited. This analysis aims to more accurately measure the direct cost of thyroid RFA in comparison to thyroid lobectomy. STUDY DESIGN: Bottom-up financial cost analysis. SETTING: Tertiary endocrine head and neck surgery center. METHODS: Time-driven activity-based costing was utilized to obtain unit-based cost estimates. The care cycles for thyroid lobectomy and RFA were defined, and process maps were developed comprising all personnel and work in the care cycle. Time estimates were calculated for all personnel involved, and public government data were used to obtain capacity cost rates for each component of the care cycle. Consumable supply and overhead costs were obtained for both procedures, and overall costs were compared. RESULTS: For thyroid lobectomy, total personnel costs were $1087.97, consumable supplies were $942.68, and overhead costs $17,199.10. For thyroid nodule RFA performed in an office setting, the total personnel cost calculated was $379.90, consumable supplies $1315.28, and overhead $7031.20. Overall, the total cost for thyroid lobectomy was $19,229.75 compared to $8726.38 for RFA. CONCLUSION: In-office thyroid nodule RFA is associated with lower direct costs than thyroid lobectomy, and overhead is the greatest cost driver for both procedures. If clinical and patient-centered outcomes are comparable, then RFA may provide higher value for appropriately selected patients.

Parathyroid Autofluorescence in Pediatric Thyroid Surgery: Experience With False Positive and False Negative Results.

Devices for near-infrared light stimulation of autofluorescence (NIRAF) allow for intraoperative identification of parathyroid glands with high sensitivity in adults. However, their performance in the pediatric population is unknown. In this case series with chart review at a tertiary academic children's hospital, we investigated pediatric patients undergoing thyroid surgery and concurrent use of a probe-based NIRAF device. Thirteen patients (ages 6-18 years) underwent thyroid and/or neck dissection procedures, and 2 patients had revision procedures for a total of 15 cases with the NIRAF device. Eight cases had NIRAF values that matched surgeon opinion of parathyroid tissue or histology when available. Six cases had false positive NIRAF readings (40.0%) and 1 case had false negative readings (6.7%). Compared with surgeon opinion or histology, the NIRAF device confirmed 26 of 34 parathyroid gland candidates (76.5%). These devices need further investigation in pediatric patients, whose tissues may have different autofluorescence characteristics.

Prognostication of papillary thyroid microcarcinoma based on preoperative ultrasound.

Background: Diagnosis of papillary thyroid microcarcinoma, defined as papillary thyroid carcinoma measuring 1cm or less in greatest diameter, has increased with improvements in ultrasound technology and widespread familiarity and utilization. Given the indolent course of papillary thyroid carcinoma, active surveillance is considered an acceptable alternative to surgical resection for select patients. Candidacy for active surveillance is determined by a number of patient and tumor characteristics. Specifically, the location of the tumor within the thyroid gland plays one of the key roles in decision making. Here we evaluate characteristics of the primary tumor and distance to the thyroid capsule in association with locoregional metastases to help guide risk assessment. Methods: Retrospective chart review of all thyroid surgeries performed by two surgeons at one medical center from 2014-2021 to evaluate characteristics of papillary thyroid microcarcinoma on preoperative ultrasound that are associated with locoregional metastatic disease. Results: Our data show a sensitivity of 65% and specificity of 95% for identifying regional metastases in papillary thyroid microcarcinoma using preoperative ultrasound. We found no correlation between regional metastasis and size of tumor, distance to thyroid capsule or trachea, tumor contour, or presence of autoimmune thyroiditis. Nodules in the superior or midpole were associated with central or lateral neck metastases, whereas nodules in the isthmus or inferior pole were only associated with central neck metastases. Conclusions: Active surveillance may be a reasonable option for even those papillary thyroid microcarcinomas adjacent to the thyroid capsule.

Ultrasound Follow-Up of Benign Thyroid Nodules: A Scoping Review.

Background: For cytologically benign thyroid nodules with very low to intermediate suspicion ultrasound patterns, optimal ultrasound follow-up intervals and outcomes of discontinuing follow-up are unclear. Methods: Ovid MEDLINE, Embase, and Cochrane Central were searched through August 2022 for studies comparing different ultrasound follow-up intervals and discontinuation versus continuation of ultrasound follow-up. The population was patients with cytologically benign thyroid nodules and very low to intermediate suspicion ultrasound patterns, and the primary outcome was missed thyroid cancers. Utilizing a scoping approach, we also included studies that were not restricted to very low to intermediate suspicion ultrasound patterns or evaluated additional outcomes such as thyroid cancer-related mortality rate, nodule growth, and subsequent procedures. Quality assessment was performed, and evidence was synthesized qualitatively. Results: One retrospective cohort study (n = 1254; 1819 nodules) compared different first follow-up ultrasound intervals for cytologically benign thyroid nodules. There was no difference between >4- versus 1- to 2-year intervals to first follow-up ultrasound in the likelihood of malignancy (0.4% [1/223] vs. 0.3% [2/715]), and no cancer-related deaths occurred. Follow-up ultrasound at >4 years was associated with increased likelihood of ≥50% nodule growth (35.0% [78/223] vs. 15.1% [108/715]), repeat fine needle aspiration (19.3% [43/223] vs. 5.6% [40/715]), and thyroidectomy (4.0% [9/223] vs. 0.8% [6/715]). The study did not describe ultrasound patterns or control for confounders, and analyses were based on interval to first follow-up ultrasound only. Other methodological limitations were not controlling for variability in follow-up duration and unclear attrition. The certainty of evidence was very low. No study compared discontinuation of ultrasound follow-up versus continuation. Conclusions: This scoping review found that evidence comparing different ultrasound follow-up intervals in patients with benign thyroid nodules is limited to one observational study, but suggests that the subsequent development of thyroid malignancies is very uncommon regardless of follow-up interval. Longer follow-up may be associated with more repeat biopsies and thyroidectomies, which could be related to more interval nodule growth that meets thresholds for further evaluation. Research is needed to clarify optimal ultrasound follow-up intervals for low to intermediate suspicion cytologically benign thyroid nodules and outcomes of discontinuing ultrasound follow-up for very low suspicion nodules.

The role of exercise-and high fat diet-induced bone marrow extracellular vesicles in stress hematopoiesis.

Exercise and obesity regulate hematopoiesis, in part through alterations in cellular and soluble components of the bone marrow niche. Extracellular vesicles (EVs) are components of the bone marrow niche that regulate hematopoiesis; however, the role of exercise training or obesity induced EVs in regulating hematopoiesis remains unknown. To address this gap, donor EVs were isolated from control diet-fed, sedentary mice (CON-SED), control diet-fed exercise trained mice (CON-EX), high fat diet-fed, sedentary mice (HFD-SED), and high fat diet-fed, exercise trained mice (HFD-EX) and injected into recipient mice undergoing stress hematopoiesis. Hematopoietic and niche cell populations were quantified, and EV miRNA cargo was evaluated. EV content did not differ between the four groups. Mice receiving HFD-EX EVs had fewer hematopoietic stem cells (HSCs) (p < 0.01), long-term HSC (p < 0.05), multipotent progenitors (p < 0.01), common myeloid progenitors (p<0.01), common lymphoid progenitors (p < 0.01), and granulocyte-macrophage progenitors (p < 0.05), compared to mice receiving HFD-SED EVs. Similarly, mice receiving EX EVs had fewer osteoprogenitor cells compared to SED (p < 0.05) but enhanced mesenchymal stromal cell (MSC) osteogenic differentiation in vitro (p < 0.05) compared to SED EVs. HFD EVs enhanced mesenchymal stromal cell (MSC) adipogenesis in vitro (p < 0.01) compared to CON EVs. HFD-EX EVs had lower microRNA-193 and microRNA-331-5p content, microRNAs implicated in inhibiting osteogenesis and leukemic cell expansion respectively, compared to HFD-SED EVs. The results identify alterations in EV cargo as a novel mechanism by which exercise training alters stress hematopoiesis and the bone marrow niche.

Sociodemographic Disparities in the Diagnostic Management of Pediatric Thyroid Nodules.

Importance: Thyroid cancer is the most common pediatric endocrine malignant neoplasm. Disparities in the workup of thyroid nodules may be significantly associated with thyroid cancer outcomes. Objective: To determine the association of sociodemographic factors with the odds of receiving a biopsy, timeliness of the procedure, and risk of nodule malignancy. Design, Setting, and Participants: This was a retrospective cross-sectional study using insurance claims data from the Optum Clinformatics Data Mart database. The study cohort comprised pediatric patients diagnosed with single thyroid nodules between 2003 and 2020. Data analysis was performed from January 1, 2003, to June 30, 2020. Main Outcomes and Measures: Multivariable logistic regression models were used to identify demographic variables associated with biopsy and nodule malignant neoplasm. A multivariable linear regression model was used to assess the time between thyroid nodule diagnosis and biopsy. Results: Of 11 643 children (median [IQR] age at diagnosis or procedure, 15 [12-17] years; 8549 [73.2%] were female and 3126 [26.8%] were male) diagnosed with single thyroid nodules, 2117 (18.2%) received a biopsy. Among the patients who received a biopsy, 304 (14.4%) were found to have a malignant nodule. Greater parental education was associated with a shorter diagnosis-to-biopsy interval (mean difference, -7.24 days; 95% CI, -13.75 to -0.73). Older age at nodule diagnosis (odds ratio [OR], 1.11; 95% CI, 1.09-1.13) and female gender (OR, 1.25; 95% CI, 1.11-1.40) were associated with increased odds of receiving a biopsy, while Black/African American (OR, 0.80; 95% CI, 0.65-0.99) and Hispanic (OR, 0.84; 95% CI, 0.72-0.99) patients had lower odds of receiving a biopsy compared with White patients. Finally, female gender (OR, 1.08; 95% CI, 0.80-1.47) was not associated with lower odds of nodule malignant neoplasm. Conclusions and Relevance: Findings of this cross-sectional study highlight disparities in the diagnostic management of pediatric thyroid nodules. These results call for future work to ensure equitable access to thyroid care for all children.

Ultrasonography of the thyroid, parathyroids, and beyond.

BACKGROUND: Ultrasonography has become an essential tool for the evaluation and management of thyroid and parathyroid diseases. Its applications extend beyond neck endocrine conditions to a multitude of pathologies within the head and neck region. OBJECTIVES: Our study aimed to: (1) provide a broad review of neck ultrasonography and key findings in neck endocrine diseases; (2) support skilled performance office-based diagnostic ultrasonography and its varied applications. MATERIALS AND METHODS: A review of the current literature was supplemented with clinical examples of key ultrasonographic findings. RESULTS: Current applications and key findings of ultrasonography in the diagnosis and management of neck endocrine conditions are reviewed. CONCLUSION: Ultrasonography is a fundamental component in the evaluation and management of neck endocrine diseases. The reader is encouraged to use this review to enhance office-based performance and application of ultrasonography.