Effects of Implementation of European Thyroid Imaging Reporting and Data System Risk Stratification in a Thyroid Cancer Program in Western Sweden: A Retrospective Cohort Study.

OBJECTIVE: The European Thyroid Imaging Reporting and Data System (EU-TIRADS) allows for selective fine needle aspiration cytology (FNAC). In 2017, EU-TIRADS was implemented as part of a nationwide standardized care bundle for thyroid cancer in Western Sweden with a population of approximately 1.7 million. The objective of this study was to investigate the clinical value of EU-TIRADS attempting to reduce the number of unnecessary FNACs in referred patients with thyroid nodules. METHODS: The study cohort consisted of all patients referred to Sahlgrenska University Hospital due to a palpable, newly detected or growing thyroid nodules or a positron emission tomography-positive finding for examination with thyroid ultrasound and selective cytology between 2018 and 2022. Medical records on EU-TIRADS classification, corresponding FNAC results, and histopathologic diagnosis were retrospectively collected. Adherence to the EU-TIRADS guidelines, use of selective FNAC, and rate of malignancy in patients who underwent surgery were assessed. RESULTS: In total, 1246 thyroid nodules in 990 patients were evaluated. The distributions of EU-TIRADS 2 to 5 (number [percentage]) for all examined nodules were 63 (5%), 462 (37%), 443 (36%), and 278 (22%), respectively. FNAC was omitted in 7% of the investigated patients. FNAC was performed in 124 nodules (10%) despite not fulfilling the EU-TIRADS criteria or absence of positron emission tomography-positive findings. The rate of malignancy was 33% and 1/50 in patients who underwent "unnecessary" FNAC. CONCLUSION: Implementation of EU-TIRADS in routine management of thyroid nodules led to the selective use of FNAC; however, the clinical impact was limited. This study provides real-world data on the value and magnitude of diagnostic improvement by implementing EU-TIRADS in clinical practice.

Impact of autofluorescence for detection of parathyroid glands during thyroidectomy on postoperative parathyroid hormone levels: parallel multicentre randomized clinical trial.

BACKGROUND: Techniques for autofluorescence have been introduced to visualize the parathyroid glands during surgery and to reduce hypoparathyroidism after thyroidectomy. METHODS: This parallel multicentre RCT investigated the use of Fluobeam® LX to visualize the parathyroid glands by autofluorescence during total thyroidectomy compared with no use. There was no restriction on the indication for surgery. Patients were randomized 1 : 1 and were blinded to the group allocation. The hypothesis was that autofluorescence enables identification and protection of the parathyroid glands during thyroidectomy. The primary endpoint was the rate of low parathyroid hormone (PTH) levels the day after surgery. RESULTS: Some 535 patients were randomized, and 486 patients received an intervention according to the study protocol, 246 in the Fluobeam® LX group and 240 in the control group. Some 64 patients (26.0 per cent) in the Fluobeam® LX group and 77 (32.1 per cent) in the control group had low levels of PTH after thyroidectomy (P = 0.141; relative risk (RR) 0.81, 95 per cent c.i. 0.61 to 1.07). Subanalysis of 174 patients undergoing central lymph node clearance showed that 15 of 82 (18 per cent) in the Fluobeam® LX group and 31 of 92 (33 per cent) in the control group had low levels of PTH on postoperative day 1 (P = 0.021; RR 0.54, 0.31 to 0.93). More parathyroid glands were identified during operation in patients who had surgery with Fluobeam® LX, and fewer parathyroid glands in the surgical specimen on definitive histopathology. No specific harm related to the use of Fluobeam® LX was reported. CONCLUSION: The use of autofluorescence during thyroidectomy did not reduce the rate of low PTH levels on postoperative day 1 in the whole group of patients. It did, however, reduce the rate in a subgroup of patients. Registration number: NCT04509011 (http://www.clinicaltrials.gov).

Revising the embryonic origin of thyroid C cells in mice and humans.

Current understanding infers a neural crest origin of thyroid C cells, the major source of calcitonin in mammals and ancestors to neuroendocrine thyroid tumors. The concept is primarily based on investigations in quail-chick chimeras involving fate mapping of neural crest cells to the ultimobranchial glands that regulate Ca(2+) homeostasis in birds, reptiles, amphibians and fishes, but whether mammalian C cell development involves a homologous ontogenetic trajectory has not been experimentally verified. With lineage tracing, we now provide direct evidence that Sox17+ anterior endoderm is the only source of differentiated C cells and their progenitors in mice. Like many gut endoderm derivatives, embryonic C cells were found to coexpress pioneer factors forkhead box (Fox) a1 and Foxa2 before neuroendocrine differentiation takes place. In the ultimobranchial body epithelium emerging from pharyngeal pouch endoderm in early organogenesis, differential Foxa1/Foxa2 expression distinguished two spatially separated pools of C cell precursors with different growth properties. A similar expression pattern was recapitulated in medullary thyroid carcinoma cells in vivo, consistent with a growth-promoting role of Foxa1. In contrast to embryonic precursor cells, C cell-derived tumor cells invading the stromal compartment downregulated Foxa2, foregoing epithelial-to-mesenchymal transition designated by loss of E-cadherin; both Foxa2 and E-cadherin were re-expressed at metastatic sites. These findings revise mammalian C cell ontogeny, expand the neuroendocrine repertoire of endoderm and redefine the boundaries of neural crest diversification. The data further underpin distinct functions of Foxa1 and Foxa2 in both embryonic and tumor development.

A 6-Week Web-Based Osteoarthritis Treatment Program: Observational Quasi-Experimental Study.

BACKGROUND: Osteoarthritis (OA) is one of the most common causes of disability, with a burden of disease estimated to increase over time. Joint Academy, a Web-based treatment for individuals with clinically verified knee or hip OA, was developed to increase access to and facilitate implementation of evidence-based nonsurgical OA treatment in accordance with international guidelines. OBJECTIVE: The primary aim of this study was to evaluate joint pain, physical function, and health-related quality of life (HRQoL) over time of users of the Joint Academy program. METHODS: We enrolled 350 patients who were recruited online and completed the initial health journal in the 6-week program. We asked patients to complete an eHealth journal and e-questionnaires, including pain level assessed by a numerical rating scale, as well as a physical function evaluation using the 30-second chair-stand test. In addition, we assessed HRQoL using the 3-level version of the EQ-5D. We also asked participants whether they experienced difficulty walking and were afraid of physical activity due to their OA and their desire for surgery. We collected descriptive data and compared pre- versus postintervention data. As a reference group, we included results retrieved from the Swedish well-structured face-to-face self-supportive OA management program Better Management of Patients With Osteoarthritis (BOA). RESULTS: Of the study cohort (n=350 patients; 239 women, mean age 62 years, mean body mass index 27 kg/m2), 71.4% (n=250) completed the program and were included in the study. We used the questionnaires to secure a clinical diagnosis of OA and to establish baseline study values. After 6 weeks of treatment, the change in mean numerical rating scale was larger than the minimal clinical difference (5.4 vs 4.1; P<.001), while physical function increased (from 10.88 to 13.14; P<.001). The percentage of participants having walking difficulties decreased from 81.7% (196/240) to 62.1% (149/240; P<.001), those afraid of being physically active decreased from 22.1% (53/240) to 6.7% (16/240; P<.001), and 22.0% (55/250) reported that they had reduced the amount of OA-related medication. After 6 weeks, 24% (13/54) of those desiring surgery at the start of the program were no longer interested. In addition, the comparison between Joint Academy and the BOA program showed similar levels of pain at 3 months, but suggested greater reduction with the use of Joint Academy due to a higher level of pain at baseline. CONCLUSIONS: The reported data suggest that participation in Joint Academy is associated with a clinically relevant decrease in pain and an increase in physical function and HRQoL, as well as a decreasing fear of physical activity. This innovative Web-based OA treatment is scalable, is population specific, and can reach a large number of individuals with impaired joints who have Internet access.

[Treatment of Graves' disease is moving towards precision medicine]. / Behandling av Graves sjukdom.

This is the first national guideline in hyperthyroidism to harmonise and update clinical practice according to what is evidence based and direct care from patients' needs. We present 4 articles in Läkartidningen of different views of the guideline, including family care perspectives, patient care perspectives and perspectives on ophthalmology. This article concerns treatment of Graves' disease and includes endocrinological, surgical and oncological perspectives on what is established practice, but also news in the national guideline that remain to be fully implemented in Sweden in the years to come. News are precision medicine using the GREAT score, preoperative calcium/D vitamin treatment, individualized levothyroxine treatment after thyroid surgery, uniformed levothyroxine replacement strategy, access to national patient information and national guidelines on radiation protection and treatment schemes for radioactive iodine. A national guideline is the creation of many persons' views, including patient representatives, and the recommendations have undergone a thorough national review process from stakeholders. It is a guideline with future perspectives for an improved care.

[Molecular diagnostics enable targeted therapies for anaplastic and poorly differentiated thyroid cancer]. / Molekylär diagnostik ger bättre behandling av tyreoideacancer.

Anaplastic and poorly differentiated thyroid cancer (ATC, PDTC) are rare and highly aggressive tumors that historically have been associated with a short life expectancy and low chance of cure. Molecular pathology and the introduction of highly effective targeted drugs have revolutionized the possibilities of management of patients with ATC and PDTC, with BRAF and MEK inhibitors as the most prominent example. Here we provide updated recommendations regarding diagnostics and management, including primary surgical management and targeted therapies based on specific molecular pathological findings.

Routine preoperative (111)In-octreotide scintigraphy in patients with medullary thyroid cancer.

BACKGROUND: Surgery is the only potential cure for patients with medullary thyroid carcinoma (MTC). Preoperative ultrasound, computed tomography and magnetic resonance imaging are not sensitive enough for detection of microscopic disease. The aim of this study was to investigate if routine preoperative (111)In-labelled (DTPA-D-Phe(1))-octreotide scintigraphy (SRS) could be used as a staging procedure in planning primary surgery in patients with MTC. METHODS: This study included patients with primary sporadic clinically overt MTC diagnosed between 1996 and 2009. All patients underwent conventional imaging of neck and thorax and SRS prior to standardised surgery. The findings on SRS were correlated to the findings on conventional imaging, histopathology and to postoperative biochemical results and survival. RESULTS: A total of 19 patients with sporadic MTC were enrolled. Median follow-up was 77(9-184) months. SRS visualised the primary tumour in 16 (84 %) patients. Fifteen (79 %) patients had locoregional lymph node metastases, but SRS detected metastatic lesions in only 8 (53 %) patients. In three patients with distant spread, SRS failed to detect metastatic lesions in two. At latest follow-up, six (32 %) patients had died, nine (47 %) patients were alive with elevated tumour markers, and four (21 %) patients were considered in complete biochemical remission. CONCLUSIONS: This study provided further evidence that SRS, compared to conventional imaging, is fairly sensitive for detection of primary MTC but not metastatic disease. Although preoperative SRS may be of prognostic value, there is no indication for its routine use as a staging procedure in planning primary surgery.

A Web-Based Platform for Patients With Osteoarthritis of the Hip and Knee: A Pilot Study.

BACKGROUND: Chronic conditions are the leading cause of disability throughout the world and the most expensive problem facing the health care systems. One such chronic condition is osteoarthritis (OA), a frequent cause of major disability. OBJECTIVE: To describe the effect on joint pain for the first users of a newly developed Web-based osteoarthritis self-managing program, Joint Academy, and to examine whether these patients would recommend other OA patients to use the program. METHODS: Patients with clinically established knee or hip OA according to national and international guidelines were recruited from an online advertisement. A trained physiotherapist screened the eligible patients by scrutinizing their answers to a standardized questionnaire. The 6-week program consisted of eight 2- to 5-minute videos with lectures about OA, effects of physical activity, self-management, and coping strategies. In addition, exercises to improve lower extremity physical function were introduced in daily video activities. During the course of the program, communication between physiotherapist and patients was based on an asynchronous chat. After 6 weeks, patients were able to continue without support from the physiotherapist. Patients reported their current pain weekly by using a numeric rating scale (range 0-10; 0=no pain, 10=worst possible pain) as long as they were in the program. In addition, after 6 weeks patients answered the question "What is the probability that you would recommend Joint Academy to a friend?" RESULTS: The eligible cohort consisted of 53 individuals (39 women; body mass index: mean 27, SD 5; age: mean 57, SD 14 years). With the continued use of the program, patients reported a constant change in pain score from mean 5.1 (SD 2.1) at baseline to mean 3.6 (SD 2.0) at week 12. Six patients participated for 30 weeks (mean 3.2, SD 2.1). Overall, the patients would highly recommend Joint Academy to other OA patients, suggesting that the platform may be useful for at least some in the vast OA population. CONCLUSIONS: Joint Academy, a Web-based platform for OA therapy, has the potential to successfully deliver individualized online treatment to many patients with OA that presently lack access to treatment.