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Metabolic rewiring is essential for tumor growth and progression to metastatic disease, yet little is known regarding how cancer cells modify their acquired metabolic programs in response to different metastatic microenvironments. We have previously shown that liver-metastatic breast cancer cells adopt an intrinsic metabolic program characterized by increased HIF-1α activity and dependence on glycolysis. Here, we confirm by in vivo stable isotope tracing analysis (SITA) that liver-metastatic breast cancer cells retain a glycolytic profile when grown as mammary tumors or liver metastases. However, hepatic metastases exhibit unique metabolic adaptations including elevated expression of genes involved in glutathione (GSH) biosynthesis and reactive oxygen species (ROS) detoxification when compared to mammary tumors. Accordingly, breast-cancer-liver-metastases exhibited enhanced de novo GSH synthesis. Confirming their increased capacity to mitigate ROS-mediated damage, liver metastases display reduced levels of 8-Oxo-2′-deoxyguanosine. Depletion of the catalytic subunit of the rate-limiting enzyme in glutathione biosynthesis, glutamate-cysteine ligase (GCLC), strongly reduced the capacity of breast cancer cells to form liver metastases, supporting the importance of these distinct metabolic adaptations.Loss of GCLC also affected the early steps of the metastatic cascade, leading to decreased numbers of circulating tumor cells (CTCs) and impaired metastasis to the liver and the lungs. Altogether, our results indicate that GSH metabolism could be targeted to prevent the dissemination of breast cancer cells.

Abstract The COVID-19 pandemic triggered the resurgence of synthetic RNA vaccine platforms allowing rapid, scalable, low-cost manufacturing, and safe administration of therapeutic vaccines. Self-amplifying mRNA (SAM), which self-replicates upon delivery into the cellular cytoplasm, leads to a strong and sustained immune response. Such mRNAs are encapsulated within lipid nanoparticles (LNPs) that act as a vehicle for delivery to the cell cytoplasm. A better understanding of LNP-mediated SAM uptake and release mechanisms in different types of cells is critical for designing effective vaccines. Here, we investigated the cellular uptake of a SAM-LNP formulation and subsequent intracellular expression of SAM in baby hamster kidney (BHK-21) cells using hyperspectral coherent anti-Stokes Raman scattering (HS-CARS) microscopy and multiphoton-excited fluorescence lifetime imaging microscopy (FLIM). Cell classification pipelines based on HS-CARS and FLIM features were developed to obtain insights on spectral and metabolic changes associated with SAM-LNPs uptake. We observed elevated lipid intensities with the HS-CARS modality in cells treated with LNPs versus PBS-treated cells, and simultaneous fluorescence images revealed SAM expression inside BHK-21 cell nuclei and cytoplasm within 5 h of treatment. In a separate experiment, we observed a strong correlation between the SAM expression and mean fluorescence lifetime of the bound NAD(P)H population. This work demonstrates the ability and significance of multimodal optical imaging techniques to assess the cellular uptake of SAM-LNPs and the subsequent changes occurring in the cellular microenvironment following the vaccine expression.

Continued population growth, increased demands for water and declining water availability are statewide water concerns in Texas. The development and movement of water from where it is to where it is needed brings with it benefits to the receiving area and concerns for the area of origin. The Vista Ridge project serves as an on-point example and case study of such concerns and processes that can mitigate, in part, negative impacts that are informative to other Texans who will soon be facing similar pressures.. Impacts on the water levels in existing wells made the Vista Ridge Project a focus of significant public discussion in 2022, including Texas House and Senate interim session hearings. This paper spotlights groundwater management issues prominent in the Vista Ridge Project that will likely be of concern with other Texas groundwater projects in the near future. These issues involve well mitigation, significant impacts from groundwater production across groundwater conservation district boundaries, meaningful consideration of nine factors in Texas Water Code §36.108(d), the balance between limiting groundwater production, development of fair share doctrines, the role of the Texas Water Development Board in the

Abstract The leadership role can be demanding and depleting. Using self-regulation and social exchange theory as a framework, we developed a three-step sequential mediation model that explains how feelings of depletion can degrade leaders’ own performance level, via the reciprocating behavior of their employees. Specifically, we hypothesized that leader depletion is negatively related to their trust beliefs. This lack of trust is expected to be reciprocated by employees in such a way that they display less citizenship behaviors towards their leader. These lowered citizenship behaviors are, in turn, predicted to negatively impact leader performance. Additionally, we hypothesized that these negative effects of feeling depleted are more pronounced for leaders who believe that their willpower is limited. Studies 1 and 2 illustrated that leader depletion indirectly influences their own performance level through leaders’ trust beliefs and employees’ leader-directed citizenship behaviors. Study 3 extended these findings from the inter-individual to the intra-individual level, and demonstrated the predicted moderating role of belief in limited willpower. Together, our studies provide new and useful insights in the broader, more distal implications of leader depletion, which have not yet been considered in existing self-regulation models.

The goal of this study was to utilize a multimodal magnetic resonance imaging (MRI) and positron emission tomography (PET) imaging approach to assess the local innate immune response in skeletal muscle and draining lymph node following vaccination in rats using two different vaccine platforms (AS01 adjuvanted protein and lipid nanoparticle (LNP) encapsulated Self-Amplifying mRNA (SAM)). MRI and 18FDG PET imaging were performed temporally at baseline, 4, 24, 48, and 72 hr post Prime and Prime-Boost vaccination in hindlimb with Cytomegalovirus (CMV) gB and pentamer proteins formulated with AS01, LNP encapsulated CMV gB protein-encoding SAM (CMV SAM), AS01 or with LNP carrier controls. Both CMV AS01 and CMV SAM resulted in a rapid MRI and PET signal enhancement in hindlimb muscles and draining popliteal lymph node reflecting innate and possibly adaptive immune response. MRI signal enhancement and total 18FDG uptake observed in the hindlimb was greater in the CMV SAM vs CMV AS01 group (↑2.3 – 4.3-fold in AUC) and the MRI signal enhancement peak and duration were temporally shifted right in the CMV SAM group following both Prime and Prime-Boost administration. While cytokine profiles were similar among groups, there was good temporal correlation only between IL-6, IL-13, and MRI/PET endpoints. Imaging mass cytometry was performed on lymph node sections at 72 hr post Prime and Prime-Boost vaccination to characterize the innate and adaptive immune cell signatures. Cell proximity analysis indicated that each follicular dendritic cell interacted with more follicular B cells in the CMV AS01 than in the CMV SAM group, supporting the stronger humoral immune response observed in the CMV AS01 group. A strong correlation between lymph node MRI T2 value and nearest-neighbor analysis of follicular dendritic cell and follicular B cells was observed (r=0.808, P

Objective: To compare long-term health-related quality of life (HRQOL) after Transoral Endoscopic Thyroidectomy Vestibular Approach (TOETVA) and transcervical approach (TCA) thyroidectomy., Study Design: Prospective cohort study., Setting: Tertiary referral center., Methods: A web-based survey was distributed to patients at our institution who met the criteria for TOETVA and underwent thyroidectomy by TOETVA or TCA between August 2017 and October 2021. All survey participants were at least 6 months postsurgery. Minors, non-English speakers, and patients who received concomitant neck dissection or reoperative thyroidectomy were excluded from the study. The survey assessed quality of life through 4 standardized instruments: the Dermatology Life Quality Index (DLQI), the Eating Assessment Tool (EAT-10), the Voice Handicap Index (VHI-10), and the Short Form Health Survey (SF-36)., Results: A total of 108 TOETVA and 129 TCA patients were included in the study. The median age of respondents was 44 (36, 54; 25th, 75th percentile) years and median time from surgery to survey was 35 (22, 45; 25th, 75th percentile) months. TOETVA group DLQI (0.63 vs 0.99; P = .17), VHI-10 (1.94 vs 1.67; P = .35), EAT-10 (2.14 vs 2.32; P = .29), SF-36 physical component (52.25 vs 51.00; P = .25), and SF-36 mental component (47.74 vs 47.29; P = .87) scores were all similar to those of the TCA group. Scrutinizing specific DLQI questions, individuals in the TOETVA group were less self-conscious of their skin as compared to the TCA group (Q2; 0.08 vs 0.26, P = .03)., Conclusion: Long-term HRQOL after TOETVA is similar to TCA, with significantly lower skin-related self-consciousness., (© 2024 The Authors. Otolaryngology–Head and Neck Surgery published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngology–Head and Neck Surgery Foundation.)

Background: Thyroglossal duct cyst (TGDC) is the most common congenital neck mass among the pediatric population. Less than 10% of the cases occur in adults. The standard of care for TGDC is surgical treatment with the Sistrunk procedure via a traditional transverse cervicotomy. This technique involves the resection of the cyst with its tract and the central portion of the hyoid bone body to avoid recurrence. The transoral vestibular approach has gained popularity as an alternative approach to open neck surgery in order to eliminate the transcervical scar associated with these procedures., Methods: We describe a case of an endoscopic Sistrunk procedure performed by the transoral vestibular approach. A scoping review of the transoral endoscopic vestibular approach Sistrunk procedure (TEVAS) was performed. The PubMed, Medline, Cochrane, Lilacs, Scielo, Mary Ann Libert and Scopus databases were systematically searched by using a Medical Subject Heading (MeSH)-optimized search strategy. The selection of papers followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines after setting inclusion and exclusion criteria., Results: The case was successful and without complications. Five studies were included in the final analysis for this review., Conclusions: This novel approach to the Sistrunk procedure is an effective alternative way to treat TGDC in selected patients who are motivated to avoid a visible neck scar., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://gs.amegroups.com/article/view/10.21037/gs-23-357/coif). M.Y.N. is a speaker for DMC. J.O.R. is a consultant for Baxter scientific and does expert testimony for Baxter scientific. The other authors have no conflicts of interest to declare., (2024 Gland Surgery. All rights reserved.)

Radiofrequency ablation (RFA) is a minimally invasive procedure performed under ultrasound guidance that offers the ability to significantly reduce the size of benign thyroid nodules. Although application for benign nodules has only emerged during the past 5 to 10 years in North America, RFA has an impressive track record of nodule reduction, compressive and cosmetic symptom improvement, and excellent safety profile without the morbidity of open surgery. The role of RFA in autonomous functioning nodules, thyroid cancer, and indeterminate nodules is controversial and remains an area of investigation., Competing Interests: Disclosure Dr J.O. Russell receives funding from a National Institutes of Health, United StatesR44 SBIR grant, is currently a site principal investigator for a clinical trial with Eli Lilly, and consults for Baxter International, Inc. Dr K.M. Frazier has no disclosures., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: We aimed to determine the prevalence and risk factors for dysphagia in adults 65 years and older before and after thyroidectomy or parathyroidectomy., Methods: We performed a longitudinal prospective cohort study of older adults undergoing initial thyroidectomy or parathyroidectomy. We administered the Dysphagia Handicap Index questionnaire preoperatively and 1, 3, and 6 months postoperatively. We compared preoperative and postoperative total and domain-specific scores using paired t tests and identified risk factors for worse postoperative scores using multivariable logistic regression., Results: Of the 175 patients evaluated, the mean age was 71.1 years (range = 65-94), 73.7% were female, 40.6% underwent thyroidectomy, 57% underwent bilateral procedures, and 21.1% had malignant diagnoses. Preoperative swallowing dysfunction was reported by 77.7%, with the prevalence 22.4% greater in frail than robust patients (P = .013). Compared to preoperative scores, 43.4% and 49.1% had worse scores at 3 and 6 months postoperatively. Mean functional domain scores increased by 62.3% at 3 months postoperatively (P = .007). Preoperative swallowing dysfunction was associated with a 3.07-fold increased likelihood of worse functional scores at 3 months. Whereas frailty was associated with preoperative dysphagia, there was no association between worse postoperative score and age, sex, race, frailty, body mass index, smoking status, gastroesophageal reflux disease, comorbidity index, malignancy, surgical extent, or type of surgery., Conclusion: Adults 65 years and older commonly report swallowing impairment preoperatively, which is associated with a 3.07-fold increased likelihood of worsened dysphagia after thyroid and parathyroid surgery that may persist up to 6 months postoperatively., (Copyright © 2023 Elsevier Inc. All rights reserved.)

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., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Treatment options for thyroid pathologies have expanded to include scarless and remote access methods such as the transoral endoscopic thyroidectomy vestibular approach (TOETVA). Currently, no standardized methods exist for locating parathyroid glands (PGs) in patients undergoing TOETVA, which can lead to parathyroid injury and subsequent hypocalcemia. This early feasibility study describes and evaluates the hANDY-i endoscopic attachment for detecting PGs in transoral thyroidectomy., Methods: We used a prototype parathyroid autofluorescence imager (hANDY-i) that was mounted to a 10-mm 0-degree endoscope. The device delivers a split screen view of Red-green-blue (RGB) and near-infrared autofluorescence (NIRAF) which allows for simultaneous anatomical localization and fluorescence visualization of PGs during endoscopic thyroid dissection., Results: One cadaveric case and two patient cases were included in this study. The endoscopic hANDY-i imaging system successfully visualized PGs during all procedures., Conclusion: The ability to leverage parathyroid autofluorescence during TOETVA may lead to improved PG localization and preservation. Further human studies are needed to assess its effect on postoperative hypocalcemia and hypoparathyroidism., Competing Interests: YK is an employee of Optosurgical LLC. RC has ownership stake in Optosurgical LLC. JR is a consultant for Baxter Scientific. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Seo, Ali, Wolfe, Nagururu, Ding, Desai, Harbison, Kim, Ning, Cha and Russell.)

Introduction: Parathyroid glands may be compromised during thyroid surgery which can lead to hypoparathyroidism and hypocalcemia. Identifying the parathyroid glands relies on the surgeon's experience and the only way to confirm their presence was through tissue biopsy. Near infrared autofluorescence technology offers an opportunity for real-time, non-invasive identification of the parathyroid glands., Methods: We used a new research prototype (hANDY-I) developed by Optosurgical, LLC. It offers coaxial excitation light and a dual-Red Green Blue/Near Infrared sensor that guides anatomical landmarks and can aid in identification of parathyroid glands by showing a combined autofluorescence and colored image simultaneously., Results: We tested the imager during 23 thyroid surgery cases, where initial clinical feasibility data showed that out of 75 parathyroid glands inspected, 71 showed strong autofluorescence signal and were correctly identified (95% accuracy) by the imager., Conclusions: The hANDY-I prototype demonstrated promising results in this feasibility study by aiding in real-time visualization of the parathyroid glands. However, further testing by conducting randomized clinical trials with a bigger sample size is required to study the effect on levels of hypoparathyroidism and hypocalcemia., Competing Interests: Author SH was employed by i2KIE LLC. Author RC has an ownership interest in Optosurgical, LLC. Authors EO and YK were employees of Optosurgical, LLC when the study was carried out. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ali, Wolfe, Nagururu, Seo, Han, Kim, Oh, Kim, Ning, Lee, Cha, Tufano and Russell.)

Background & Aims: Fibrosis and tissue stiffening are hallmarks of inflammatory bowel disease (IBD). We have hypothesized that the increased stiffness directly contributes to the dysregulation of the epithelial cell homeostasis in IBD. Here, we aim to determine the impact of tissue stiffening on the fate and function of the intestinal stem cells (ISCs)., Methods: We developed a long-term culture system consisting of 2.5-dimensional intestinal organoids grown on a hydrogel matrix with tunable stiffness. Single-cell RNA sequencing provided stiffness-regulated transcriptional signatures of the ISCs and their differentiated progeny. YAP-knockout and YAP-overexpression mice were used to manipulate YAP expression. In addition, we analyzed colon samples from murine colitis models and human IBD samples to assess the impact of stiffness on ISCs in vivo., Results: We demonstrated that increasing the stiffness potently reduced the population of LGR5 + ISCs and KI-67 + -proliferating cells. Conversely, cells expressing the stem cell marker, olfactomedin-4, became dominant in the crypt-like compartments and pervaded the villus-like regions. Concomitantly, stiffening prompted the ISCs to preferentially differentiate toward goblet cells. Mechanistically, stiffening increased the expression of cytosolic YAP, driving the extension of olfactomedin-4 + cells into the villus-like regions, while it induced the nuclear translocation of YAP, leading to preferential differentiation of ISCs toward goblet cells. Furthermore, analysis of colon samples from murine colitis models and patients with IBD demonstrated cellular and molecular remodeling reminiscent of those observed in vitro., Conclusions: Collectively, our findings highlight that matrix stiffness potently regulates the stemness of ISCs and their differentiation trajectory, supporting the hypothesis that fibrosis-induced gut stiffening plays a direct role in epithelial remodeling in IBD., (Copyright © 2023 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Introduction: thyroid surgery through the transoral vestibular approach is a reality in many countries. While several competing remote access techniques have been developed in the last 20 years, many were not reproducible. Transoral Endoscopic Neck Surgery (TNS) has been shown to be reproducible in different centers around the world, and approximately five years after its description it has been adopted relatively quickly for various reasons. To date, there are at least 7 Brazilian studies published, including a series of more than 400 cases. The aim of this work is to study the progression of Transoral Neck Surgery in Brazil and describe the profile of surgeons involved in this new approach., Methods: this is a retrospective study with descriptive statistics. A REDCap based survey about transoral endoscopic thyroidectomy and parathyroidectomy vestibular approach (TOETVA/TOEPVA) was done with 66 Brazilian surgeons regarding surgeon profile, numbers of cases performed by geographic region, what kind of training was necessary prior to the first case and behavior of the surgeon proposing these new approaches., Results: response rate of this survey was 53%. To date, 1275 TOETVA/TOEPVA cases had been performed in Brazil, 1229 thyroidectomies (96.4%), 42 parathyroidectomies (3.3%) and 4 combined procedures (0.3%). Most of the cases were done in the southeast region (821, 64.4%), 538 (42.2%) cases in the State of São Paulo and 283 (22.2%) cases in the State of Rio de Janeiro., Conclusions: TOETVA is becoming popular in Brazil. Younger surgeons, especially those between 30 and 50 years old were more likely to adopt this approach.

Objective: To investigate indications, surgical and functional outcomes of robotic or endoscopic facelift thyroid surgery (FTS) and whether FTS reported comparable outcomes of other surgical approaches., Data Sources: PubMed, Cochrane Library, and Scopus., Review Methods: A literature search was conducted about indications, clinical and surgical outcomes of patients who underwent FTS using PICOTS and PRISMA Statements. Outcomes reviewed included age; gender; indications; pathology; functional evaluations; surgical outcomes and complications., Results: Fifteen papers met our inclusion criteria, accounting for 394 patients. Endoscopic or robotic FTS was carried out for benign and malignant thyroid lesions, with or without central neck dissection. Nodule size and thyroid lobe volume did not exceed 6, 10 cm, respectively. FTS reported comparable outcome with transaxillary or oral approaches about operative time, complication rates or drainage features. The mean operative time ranged from 88 to 220 min, depending on the type of surgery (endoscopic vs robotic hemi- or total thyroidectomy). Conversion to open surgery was rare, occurring in 0-6.3% of cases. The most common complications were earlobe hypoesthesia, hematoma, seroma, transient hypocalcemia and transient recurrent nerve palsy. There was an important disparity between studies about the inclusion/exclusion criteria, surgical and functional outcomes., Conclusion: FTS is a safe and effective approach for thyroid benign and malignant lesions. FTS reports similar complications to conventional thyroidectomy and excellent cosmetic satisfaction., (© 2023. The Author(s).)

Introduction: Hypoparathyroidism and hypocalcemia are common complications after thyroid surgery. Parathyroids may be incidentally damaged or removed because they are difficult to distinguish from surrounding tissue. Intraoperative optical technologies such as near infrared autofluorescence (NIRAF) are becoming increasingly popular to help identify parathyroids during thyroid surgery. The objective of this video is to introduce a developing NIRAF device called hANDY-i and compare the device with existing Food and Drug Administration approved technology., Materials and Methods: hANDY-i is developed by Optosurgical, LLC. The device consists of a coaxial 785 nm laser excitation module and coregistred red-green-blue and near-infrared cameras. Operation of the device and output from preliminary intraoperative use are shown., Results: hANDY-i performs well, producing intuitive side-by-side NIRAF and RGB images of the operating field. The device demonstrates high contrast between suspected parathyroid glands and surrounding tissue. Operating theater, overhead lamps, and surgical headlights can all be used with the device. The device is also shown to be effective in both in vivo and ex vivo applications., Conclusions: The prototype described advance NIRAF technology by reducing light sensitivity and improving output representation. In doing so, hANDY-i makes NIRAF more accessible and less obstructive to the surgical workflow., Sources of Funding: This study was supported by the National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health under Award Number R43EB030874., Disclaimer: The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.Yoseph Kim is an employee of Optosurgical LLC. Jaepyeong Cha has ownership stake in Optosurgical LLC. For all other authors, no competing financial interests exist.Runtime of video: 7 mins 14 secs., (Copyright 2023, Mary Ann Liebert, Inc. and American Thyroid Association.)

Well differentiated thyroid cancer is a common malignancy diagnosed in young patients. The prognosis tends to be excellent, so years of survivorship is expected with low risk disease. When making treatment decisions, physicians should consider long-term quality of life outcomes when guiding patients. The implications for treating indolent, slow growing tumors are immense and warrant careful consideration for the functioning years ahead. Surgery is the standard of care for most patients, however for a subset of patients, active surveillance is appropriate. For those wishing to treat their cancer in a more active way, novel remote access approaches have emerged to avoid a cervical incision. In the era of "doing less", options have further expanded to include minimally invasive approaches, such as radiofrequency ablation that avoids an incision, time off work, a general anesthetic, and the possibility of post-treatment hypothyroidism. In this narrative review, we examine the health related quality of life effects that surgery has on patients with thyroid cancer, including some of the newer innovations that have been developed to address patient concerns. We also review the impact that less aggressive treatment has on patient care and overall wellbeing in terms of active surveillance, reduced doses of radioactive iodine (RAI) treatment, or minimally invasive techniques such as radiofrequency ablation (RFA) for low risk thyroid disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Pace-Asciak, Russell and Tufano.)

Background: There is an increasing array of treatment options for addressing clinically significant thyroid nodules, including radiofrequency ablation (RFA). While effective, the cost compared to alternative approaches has not been well elucidated., Methods: This study involved a retrospective chart review, focusing on variable direct cost (VDC) of each procedure, from April 2016 to January 2020. We analyzed costs for 53 open lobectomies and 16 RFA procedures., Results: Cost effectiveness depended on the simulated cost of the RFA probe. In comparison to open lobectomy, the VDC to perform RFA was $597 (19%) cheaper when the simulated probe cost was $1500 and $403 (13%) more expensive for a probe cost of $2500. Statistical significance was achieved for both these differences., Conclusions: If cost per RFA probe can be less than $2100-the break-even dollar amount between open lobectomy and RFA-there would be considerable cost savings for treating thyroid nodules., (© 2022 Wiley Periodicals LLC.)

Thyroid surgery is one of the most common head and neck procedures. The thyroid can be accessed through an anterior cervical incision, or by remote access techniques such as the transoral endoscopic thyroidectomy vestibular approach (TOETVA) which is favored for its ease, safety and direct plane to the thyroid gland. Other novel approaches for targeting small-localized well-differentiated thyroid cancer are by thermal ablation, namely ultrasound guided radiofrequency ablation. These innovative techniques for minimizing a cutaneous scar or for targeting small cancers directly without removal of the gland have developed alongside our realization that low risk well-differentiated thyroid cancer tends to be slow growing and indolent. Up to date, the most robust data supports offering these therapies primarily to patients who would be eligible for active surveillance protocols. In this paper, we review the traditional surgical approaches for removing well-differentiated thyroid cancer, as well as innovative remote access techniques (namely TOETVA), and minimally invasive thermal ablation (namely RFA)., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022. Published by Elsevier Ltd.)

Background: Radiofrequency ablation (RFA) has been recently adopted into the practice of thyroidology in the United States, although its use as an alternative to traditional thyroid surgery in Asia and Europe came near the turn of the 21st century. In the United States, only a few studies with small sample sizes have been published to date. We examined outcomes of benign thyroid nodules treated with RFA from 2 North American institutions., Methods: We performed a prospective, multi-institutional cohort study of thyroid nodules treated with RFA between July 2019 and January 2022. Demographics, sonographic characteristics of thyroid nodules, thyroid function profiles, procedural details, complications, and nodule volume measurements at 1, 3, 6, and 12 months follow-up were evaluated. Adjusted multivariate logistic regression analysis was performed to identify sonographic features associated with treatment failure., Results: A total of 233 nodules were included. The median and interquartile range of volume reduction rate (VRR) at 1, 3, 6, and 12 months were 54% [interquartile range (IQR): 36%-73%], 58% (IQR: 37%-80%), 73% (IQR: 51%-90%), and 76% (IQR: 52%-90%), respectively ( P <0.001). Four patients presented with toxic adenomas. All patients were confirmed euthyroid at 3-month postprocedure follow-up. Two patients developed temporary hoarseness of voice, but no hematoma or nodular rupture occurred postprocedure. Elastography was significantly associated with VRR. Compared with soft nodules, stiff nodules were more likely to have a lower VRR (odds ratio: 11.64, 95% confidence interval: 3.81-35.53, P <0.05), and mixed elasticity was also more likely to have a lower VRR (odds ratio: 4.9; 95% confidence interval: 1.62-14.85, P <0.05)., Conclusions: This is the largest multi-institutional North American study examining thyroid nodule treatment response to RFA. RFA is a safe and effective treatment option that allows preservation of thyroid function with minimal risk of procedural complications., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Papillary thyroid carcinomas (PTCs) account for most endocrine tumors; however, screening and diagnosing the recurrence of PTC remains a clinical challenge. Using microRNA sequencing (miR-seq) to explore miRNA expression profiles in PTC tissues and adjacent normal tissues, we aimed to determine which miRNAs may be associated with PTC recurrence and metastasis. Public databases such as TCGA and GEO were utilized for data sourcing and external validation, respectively, and miR-seq results were validated using quantitative real-time PCR (qRT-PCR). We found miR-145 to be significantly downregulated in tumor tissues and blood. Deregulation was significantly related to clinicopathological features of PTC patients including tumor size, lymph node metastasis, TNM stage, and recurrence. In silico data analysis showed that miR-145 can negatively regulate multiple genes in the TC signaling pathway and was associated with cell apoptosis, proliferation, stem cell differentiation, angiogenesis, and metastasis. Taken together, the current study suggests that miR-145 may be a biomarker for PTC recurrence. Further mechanistic studies are required to uncover its cellular roles in this regard.

Early and precise detection of parathyroid glands (PGs) is a challenging problem in thyroidectomy due to their small size and similar appearance to surrounding tissues. Near-infrared autofluorescence (NIRAF) has stimulated interest as a method to localize PGs. However, high incidence of false positives for PGs has been reported with this technique. We introduce a prototype equipped with a coaxial excitation light (785 nm) and a dual-sensor to address the issue of false positives with the NIRAF technique. We test the clinical feasibility of our prototype in situ and ex vivo using sterile drapes on 10 human subjects. Video data (1287 images) of detected PGs were collected to train, validate and compare the performance for PG detection. We achieved a mean average precision of 94.7% and a 19.5-millisecond processing time/detection. This feasibility study supports the effectiveness of the optical design and may open new doors for a deep learning-based PG detection method., (© 2022 Wiley-VCH GmbH.)

Pain management is an important consideration for Head and Neck Cancer (HNC) patients as they are at an increased risk of developing chronic opioid use, which can negatively impact both quality of life and survival outcomes. This retrospective cohort study aimed to evaluate pain, opioid use and opioid prescriptions following HNC surgery. Participants included patients undergoing resection of a head and neck tumor from 2019-2020 at a single academic center with a length of admission (LOA) of at least 24 h. Exclusion criteria were a history of chronic pain, substance-use disorder, inability to tolerate multimodal analgesia or a significant post-operative complication. Subjects were compared by primary surgical site: Neck (neck dissection, thyroidectomy or parotidectomy), Mucosal (resection of tumor of upper aerodigestive tract, excluding oropharynx), Oropharyngeal (OP) and Free flap (FF). Average daily pain and total daily opioid consumption (as morphine milligram equivalents, MME) and quantity of opioids prescribed at discharge were compared. A total of 216 patients met criteria. Pain severity and daily opioid consumption were comparable across groups on post-operative day 1, but both metrics were significantly greater in the OP group on the day prior to discharge (DpDC) (5.6 (1.9-8.6), p < 0.05; 49 ± 44 MME/day, p < 0.01). The quantity of opioids prescribed at discharge was associated with opioid consumption on the DpDC only in the Mucosal and FF groups, which had longer LOA (6-7 days) than the Neck and OP groups (1 day, p < 0.001). Overall, 65% of patients required at least one dose of an opioid on the DpDC, yet 76% of patients received a prescription for an opioid medication at discharge. A longer LOA (aOR = 0.82, 95% CI: 0.63-0.98) and higher Charlson Comorbidity Index (aOR = 0.08, 95% CI: 0.01-0.48) were negatively associated with receiving an opioid prescription at the time of discharge despite no opioid use on the DpDC, respectively. HNC patients, particularly those with shorter LOA, may be prescribed opioids in excess of their post-operative needs, highlighting the need the for improved pain management algorithms in this patient population. Future work aims to use prospective surveys to better define post-operative and outpatient pain and opioid requirements following HNC surgery., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Trakimas, Perez-Heydrich, Mandal, Tan, Gourin, Fakhry, Koch, Russell, Tufano, Eisele and Vosler.)

Importance: The transoral vestibular approach for thyroid and parathyroid surgery is being adopted rapidly world-wide. Currently there is a paucity of information on this approach for primary hyperparathyroidism (PHPTH). If this approach is safe and efficacious it would provide patients a completely scarless option for parathyroidectomy., Objective: To determine whether parathyroidectomy via the transoral vestibular approach can be successfully done in a safe and efficient manner., Design: Consecutive case series of 101 transoral parathyroidectomies performed over a two-year period., Setting: Multi-institutional, academic, high-volume transoral thyroidectomy centers from the USA, Israel, and Thailand., Participants: A consecutive series of adult patients with a biochemical diagnosis of classic PHPTH and who met criteria for parathyroidectomy based on established international consensus for surgery for PHPTH. All patients also had well-localized single adenomas on at least two preoperative imaging studies., Intervention: Transoral endoscopic parathyroidectomy vestibular approach., Main Outcomes and Measures: Surgical success rate defined by immediate intra or post-operative return to normal PTH values. Surgical complications including recurrent laryngeal nerve injury, permanent hypoparathyroidism, and infection., Results: Of the 101 consecutive transoral parathyroidectomy patients 84% were female with an average age of 54.23 ± 11.0 years and an average BMI of 27.35 ± 6.19. Ninety-nine out of the 101 patients had immediate return to normal PTH after resection for a surgical success rate of 98%. There were no permanent recurrent laryngeal nerve injuries, one temporary nerve palsy, and no permanent hypoparathyroidism. The median operative time dropped from 130.5 min (IQR 86) to 66.5 min (IQR 56) between the first- and second-half of cases., Conclusion and Relevance: Transoral endoscopic parathyroidectomy via the vestibular approach is a scarless method of removing parathyroids that is clinically feasible, safe, and efficacious and is a reasonable option for focused minimally invasive parathyroidectomy that can be offered to select patients with PHPTH., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Ultrasound-guided radiofrequency ablation has shown promising results for nonsurgical treatment of benign thyroid nodules. The purpose of this study is to investigate public perceptions of radiofrequency ablation and identify salient decision factors for benign thyroid nodules treatment., Methods: An internet-based survey was distributed via an online platform. Survey participants were prompted to envision having a benign thyroid nodules and were assessed on risk acceptance, willingness to pay, and importance of decision factors (eg, cost, risk, scarring) regarding treatment with either radiofrequency ablation or standard surgery., Results: A total of 830 respondents (male 46.3%, median age 35 years) were included. Respondents ranked the most important factors for benign thyroid nodules treatment as risk of missing cancer and risk of permanent hoarseness (mean score 5.23 and 4.50 out of 7, respectively). Female respondents ranked missing cancer higher in importance compared with other decision factors (coefficient = 0.251, P = .0002). Younger respondents (coefficient = 0.009, P = .014) or those with higher education levels (coefficient = 0.092, P = .010) ranked having a scar as a more important decision factor. Prior scars were associated with choosing a nonsurgical procedure over surgery (coefficient = 0.478, P = .00), even if scars were well-healed (coefficient = 0.781, P < .0001). On average, respondents are willing to pay less for radiofrequency ablation than for standard surgery (radiofrequency ablation: $7,612.44 vs surgery: $8,298.50; P < .0001)., Conclusion: Respondents identified risk of missing cancer and risk of permanent hoarseness as the most important decision factors for benign thyroid nodules treatment. Education level and history of previous scars are both associated with a proclivity toward nonsurgical treatment and radiofrequency ablation., (Copyright © 2022 Elsevier Inc. All rights reserved.)

In the past decade, there has seen been a shift from treating all thyroid cancer surgically, to favoring less aggressive approaches for low-risk thyroid cancer. Surgery was historically the treatment of choice for most thyroid cancer. Active surveillance has emerged as an alternative for low-risk thyroid cancer in select patients. This approach has been accepted worldwide, and sound evidence supports its oncological safety in carefully selected patients. However, not all patients want to undergo lifelong monitoring, and some patients may wish to treat their cancer in a minimally invasive manner. Thermal ablation has developed as a minimally invasive alternative to surgery and active surveillance for well selected patients with thyroid malignancy. Herein, we review the role of thermally ablative techniques, specifically radiofrequency ablation, for the treatment of small primary thyroid cancers, recurrent thyroid cancer, and lymph node metastases., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

The field of endocrine surgery has expanded from the traditional open neck approach to include remote access techniques as well as minimally invasive approaches for benign and malignant thyroid nodules. In experienced hands and with careful patient selection, each approach is considered safe, however complications can and do exist. Post-operative dysphonia can have serious consequences to the patient by affecting quality of life and ability to function at work and in daily life. Given the significance of post-procedural dysphonia, we review the surgical and non-surgical techniques for minimizing and treating recurrent laryngeal nerve injury that can be utilized with the traditional open neck approach, remote access thyroidectomy, or minimally invasive thermal ablation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Pace-Asciak, Russell and Tufano.)

The Hippo signalling pathway has emerged as a major player in many aspects of liver biology, such as development, cell fate determination, homeostatic function and regeneration from injury. The regulation of Hippo signalling is complex, with activation of the pathway by diverse upstream inputs including signals from cellular adhesion, mechanotransduction and crosstalk with other signalling pathways. Pathological activation of the downstream transcriptional co-activators yes-associated protein 1 (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ, encoded by WWTR1), which are negatively regulated by Hippo signalling, has been implicated in multiple aspects of chronic liver disease, such as the development of liver fibrosis and tumorigenesis. Thus, development of pharmacological inhibitors of YAP-TAZ signalling has been an area of great interest. In this Review, we summarize the diverse roles of Hippo signalling in liver biology and highlight areas where outstanding questions remain to be investigated. Greater understanding of the mechanisms of Hippo signalling in liver function should help facilitate the development of novel therapies for the treatment of liver disease., (© 2022. Springer Nature Limited.)

Objective: Autonomously functioning thyroid nodules (AFTNs) have long been treated with either surgery or radioactive iodine (RAI). Being an invasive procedure, even thyroid lobectomy for this condition is associated with complications such as anesthesia side effects, scarring, iatrogenic hypothyroidism, and injury to other structures. Similarly, RAI is associated with hypothyroidism and may require multiple courses. Therefore, minimally invasive techniques such as radiofrequency ablation (RFA) are being advocated as an alternative treatment for AFTNs. To date, only few studies have been published on this topic and are largely on European and Asian populations. The aim of this review is to assess the efficacy and safety of RFA as a potential alternative for treatment of AFTNs compared to conventional surgery and radioiodine., Methods/study Design: Comprehensive PubMed and Embase searches were performed using the following terms such as (autonomously functioning thyroid nodules and radiofrequency ablation), (radiofrequency ablation and hyperthyroidism), and (radiofrequency ablation and toxic thyroid nodule). Both prospective and retrospective studies were included based on the inclusion and exclusion criteria specified in the text., Results: Initially, 57 studies were identified and after excluding 47 studies, finally 10 studies were included in the review., Conclusion: Although surgery remains the first line treatment for AFTN. However, RFA is a safe option compared to RAI or surgery, especially in patients who are high-risk surgical candidates or have absolute contraindications to RAI. Currently, trials with follow-up greater than or equal to 5 years are warranted. It will aid in formulating a standardized surveillance protocol and also generalize RFA's use for AFTN. Laryngoscope, 132:906-914, 2022., (© 2021 The American Laryngological, Rhinological and Otological Society, Inc.)

Introduction: A cervical scar has been shown to have an impact on the quality of life of children undergoing thyroid surgery. Transoral endoscopic vestibular thyroidectomy via the vestibular approach (TOETVA) offers the absence of a cutaneous incision, and has not been described to date in the pediatric population., Objective: To describe the first series of TOETVA in a pediatric population., Patients and Methods: A retrospective, multicenter study, including all patients > 18 years old who underwent TOETVA. Data was prospectively collected and included demographics, preoperative ultrasound, cytology and indications for surgery. Intraoperative parameters included length of surgery and complications, with final pathology and postoperative course also reviewed. TOETVA surgical success was defined as completion of surgery via this approach., Results: Forty-eight children were included. Of these, 43 (89.5%) were girls. The median age was 16 years (range 10-17). The most common indication for surgery was a benign thyroid nodule (n = 26, 54.1%). Eleven patients (22.9%) had papillary thyroid carcinoma on final pathology, of which 90.9% (10/11) were diagnosed pre-operatively based on FNA cytology. Hemithyroidectomy was performed in 36 patients (75%). All surgeries were completed endoscopically. The mean malignant tumor size was 1.4 ± 0.4 cm and all tumors were completely excised with clean margins. No permanent complications were documented. A single patient (2.1%) had transient RLN injury (1.6%, 1/60 nerves at risk). Transient hypocalcemia was documented in 4 of the 12 patients undergoing total thyroidectomy (33.3%). Transient mental nerve injury/chin hypoesthesia was documented in 2 patients (4.2%)., Conclusions: TOETVA appears to be a feasible and safe approach for thyroidectomy in the pediatric population in carefully selected cases, and may be discussed with patients and parents as an alternative for the trans-cervical approach., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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., (© 2021 Wiley Periodicals LLC.)

Continuous and intermittent intraoperative nerve monitoring (IONM) has become an important asset for endocrine surgeons over the past few decades. The ability to determine neurophysiologic integrity of the recurrent laryngeal nerve (RLN) and external branch of the superior laryngeal nerve (EBSLN) on top of identification and meticulous dissection of the nerve in the surgical field, has allowed for advances in technology and improved outcomes when it comes to prevention of vocal fold immobility. This article aims to compare in review continuous and intermittent nerve monitoring (CIONM, IIONM), as well as review the current paradigms of their use. This article will also discuss the future of intraoperative nerve monitoring technologies in scarless thyroid surgery and percutaneous approaches to thyroid pathology in form of radiofrequency ablation (RFA)., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Pace-Asciak, Russell and Dhillon.)

Background: Thyroid nodules are commonly being diagnosed in general population and have a potential for malignant transformation. Historically, surgery has been considered as the first line treatment for these tumors. However, with passage of time newer minimally invasive techniques such as RFA (radiofrequency ablation) has been adapted. Though, RFA for thyroid tumors has been performed more commonly in Asian and European countries, it is a fairly new technique in North America. The aim of the review is to assess the current data and conclude that whether RFA is likely a valuable option when compared to surgery for treatment of thyroid tumors., Materials and Methods: A Comprehensive PubMed/MEDLINE, Embase and Web of Science search was performed. To expand our search, references of the retrieved articles were also screened for additional data. After selecting the studies that fulfilled the initial screening, authors independently reviewed the selected studies and screened the full texts to identify those that met the inclusion criteria., Results: The comprehensive literature search from PubMed/MEDLINE, Web of Science, and EMBASE databases revealed 1094 studies (Embase 870, PubMed 200, and Web of Science 24). References were imported for screening. Amongst 1094 studies, 138 duplicates removed, and 956 studies were screened against title and abstract. After these 777 studies were excluded the remaining 179 studies were assessed for full-text eligibility. Amongst them 127 studies excluded due to wrong design or setting. Finally, 18 studies were included in the review., Conclusion: RFA appears to be a safe alternative to surgery in selected cases. However, it is not widely used and there are few randomized controlled trials. Furthermore, it is associated with a low risk profile and has shown promising results in patients who are difficult surgery candidates. Currently large-scale prospective studies are needed in North America to establish the efficacy of RFA and its use as an alternative to surgery for thyroid tumors., (Copyright © 2021 Elsevier Inc. All rights reserved.)