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Context: The active surveillance (AS) program for papillary thyroid carcinoma (≤1 cm) at low risk (mPTC) showed a low percentage of progression., Objective: The aim of this study was to find a molecular signature of cases that showed disease progression during AS, which would allow their early identification., Methods: We performed next-generation sequencing of 95 fine-needle aspiration cytology specimens from cases prospectively enrolled in the AS program to analyze key somatic driver alterations or gene fusions implicated in PTC tumorigenesis. TERT promoter analysis was performed using Sanger sequencing or droplet digital polymerase chain reaction., Results: BRAF p.V600E was found in 66.3% (63/95) of mPTC and was the most common somatic alteration, followed by RAS oncogene mutations detected in 3.2% of mPTC (3/95: 2 NRAS and 1 KRAS) and gene fusions detected in 3.2% of mPTC (3/95: 1 RET-PTC1, 1 TFG-NTRK1, 1 ALK imbalance). No TERT promoter mutations (C228T and C250T) were found in the analyzed mPTC (84/95). The comparison between the molecular profile and the clinical outcome of the mPTC (stable vs progressive disease) showed no correlation (P = .6) and did not identify a molecular signature able to identify progressive mPTC., Conclusion: The molecular profile of mPTC is like that of bigger PTC with the exception that none of them showed a TERT promoter mutation. The identification of the most common driver mutations, such as BRAF, RAS, or gene fusions, is not helpful for the early identification of mPTC that will show disease progression during follow-up in the AS program., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. See the journal About page for additional terms.)

Objective: The purpose of this study was to develop a data-driven Bayesian network approach to understand the potential multivariate pathways of the effect of manual physical therapy in women with carpal tunnel syndrome (CTS)., Methods: Data from a randomized clinical trial (n = 104) were analyzed comparing manual therapy including desensitization maneuvers of the central nervous system versus surgery in women with CTS. All variables included in the original trial were included in a Bayesian network to explore its multivariate relationship. The model was used to quantify the direct and indirect pathways of the effect of physical therapy and surgery on short-term, mid-term, and long-term changes in the clinical variables of pain, related function, and symptom severity., Results: Manual physical therapy improved function in women with CTS (between-groups difference: 0.09; 95% CI = 0.07 to 0.11). The Bayesian network showed that early improvements (at 1 month) in function and symptom severity led to long-term (at 12 months) changes in related disability both directly and via complex pathways involving baseline pain intensity and depression levels. Additionally, women with moderate CTS had 0.14-point (95% CI = 0.11 to 0.17 point) poorer function at 12 months than those with mild CTS and 0.12-point (95% CI = 0.09 to 0.15 point) poorer function at 12 months than those with severe CTS., Conclusion: Current findings suggest that short-term benefits in function and symptom severity observed after manual therapy/surgery were associated with long-term improvements in function, but mechanisms driving these effects interact with depression levels and severity as assessed using electromyography. Nevertheless, it should be noted that between-group differences depending on severity determined using electromyography were small, and the clinical relevance is elusive. Further data-driven analyses involving a broad range of biopsychosocial variables are recommended to fully understand the pathways underpinning CTS treatment effects., Impact: Short-term effects of physical manual therapy seem to be clinically relevant for obtaining long-term effects in women with CTS., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Physical Therapy Association. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Context: Clinical management of patients with thyroid nodules indeterminate at fine-needle aspiration (FNA) cytology is still unsettled., Objective: Our objective was to establish the clinical outcome of patients with thyroid nodules indeterminate at cytology and to identify the features associated with malignancy., Design and Patients: This was a retrospective evaluation of 1520 consecutive patients with indeterminate cytology among 100 065 patients who underwent FNA between January 2000 and December 2010., Results: Of 1520 patients, 371 (24.4 %) had thyroid cancer at histology, the follicular variant of papillary cancer being the most frequent histotype, and 342 patients with cancer were free of disease after thyroidectomy and (131)I remnant ablation, whereas 29 needed further treatment because of persistent disease. Among them, only 12 had persistence of disease at the end of follow-up. Atypias at cytology (P = .001), blurred nodule margins (P = .005), and spot microcalcifications (P = .003) at thyroid ultrasound (US) were significantly associated with malignancy. A clinical score including cytology and US characteristics was calculated; the lowest value showed a high negative predictive value (83.9%) for the presence of malignancy and even higher (99.5%) for the presence of a more cumbersome cancer disease, and only 4 of the 29 patients who needed further treatment were included in the group with the lowest risk score., Conclusions: Patients with Thy 3 cytology and histology of thyroid cancer had an overall good prognosis. A clinical risk score including the results of cytology and US features is helpful in the management of patients with indeterminate thyroid nodules.

Models for genome-wide prediction and association studies usually target a single phenotypic trait. However, in animal and plant genetics it is common to record information on multiple phenotypes for each individual that will be genotyped. Modeling traits individually disregards the fact that they are most likely associated due to pleiotropy and shared biological basis, thus providing only a partial, confounded view of genetic effects and phenotypic interactions. In this article we use data from a Multiparent Advanced Generation Inter-Cross (MAGIC) winter wheat population to explore Bayesian networks as a convenient and interpretable framework for the simultaneous modeling of multiple quantitative traits. We show that they are equivalent to multivariate genetic best linear unbiased prediction (GBLUP) and that they are competitive with single-trait elastic net and single-trait GBLUP in predictive performance. Finally, we discuss their relationship with other additive-effects models and their advantages in inference and interpretation. MAGIC populations provide an ideal setting for this kind of investigation because the very low population structure and large sample size result in predictive models with good power and limited confounding due to relatedness., (Copyright © 2014 by the Genetics Society of America.)

Context: The mechanisms linking thyroid autoimmunity and iodine use in humans are unknown., Objective: Our aim was to correlate iodine intake, thyroid autoimmunity, and recognition of thyroglobulin (Tg) epitopes after implementation of iodine prophylaxis., Setting: The general community living in an Italian village was evaluated., Main Outcome Measures: Thyroglobulin autoantibodies (TgAb), thyroperoxidase autoantibodies (TPOAb), and urinary iodine excretion were assessed in 906 iodized salt users (IS-users) and 389 nonusers (IS-nonusers). Ultrasound (US) was performed to identify thyroid hypoechogenicity, suggestive of Hashimoto thyroiditis (HT). TgAb epitope pattern in 16 IS-users and 17 IS-nonusers was evaluated by an inhibition binding assay to Tg, using human monoclonal TgAb-Fab directed to A, B, C, and D epitopes on Tg., Results: Median urinary iodine excretion was slightly higher in IS-users than in IS-nonusers (112.0 μg/L vs 86.5 μg/L; P < .01). TgAb, and not TPOAb, was more frequent in IS-users (18.9% vs 13.6%, P = .02). HT-US was found in 87 subjects, among whom both positive TgAb (58.4% vs 31.8%, P = .03) and TPOAb (61.5% vs 45.4%. P = .04) were more frequent in IS-users. In this group significantly higher serum levels of TgAb (median 108 U/mL vs 30 U/mL; P = .02), but not of TPOAb, were present. Iodized salt use had no effect on the 1208 non HT-US subjects. TgAb directed to the epitope B of Tg were more frequent in IS-users than in IS-nonusers (27.5% vs 3.0%, P = .047)., Conclusions: Iodine-induced thyroid autoimmunity is related to TgAb and the unmasking of a cryptic epitope on Tg contributes to this relationship in humans.

Background: Indeterminate and nondiagnostic patterns represent the main limitation of fine-needle aspiration (FNA) cytology of thyroid nodules, clinical and echographic features being poorly predictive of malignancy. The newly developed real-time ultrasound elastography (USE) has been previously applied to differentiate malignant from benign lesions. The aim of this study was to get further insights into the role of USE in the presurgical diagnosis of nodules with indeterminate or nondiagnostic cytology., Patients: The study included 176 patients who had one (n=138) or multiple (n=38) nodules with indeterminate or nondiagnostic cytology on FNA, for whom histology was available after thyroidectomy. A total of 195 nodules (142 indeterminate, 53 nondiagnostic) were submitted to USE, and elasticity was scored as 1 (high), 2 (intermediate), or 3 (low)., Results: In indeterminate lesions, the score 1, describing high elasticity, was strongly predictive of benignity, being found in 102 of 111 benign nodules and in only one of 31 carcinomas (P<0.0001). By combining the scores 2 and 3, USE had a sensitivity of 96.8% and a specificity of 91.8%. In nodules with nondiagnostic cytology, score 1 was found in 39 of 45 benign nodules and in only one of eight carcinomas (P<0.0001). By combining the scores 2 and 3, USE had a sensitivity of 87.5% and a specificity of 86.7%., Conclusions: USE may represent an important tool for the diagnosis of thyroid cancer in nodules with indeterminate or nondiagnostic cytology and may prove useful in selecting patients who are candidates for surgery.

Objective: To evaluate the risk of papillary thyroid carcinoma (PTC) at fine-needle aspiration (FNA) cytology in 34 120 patients., Results: False positive and false negative rates of FNA cytology were 1.2 and 1.8% in comparison with the histology in 3406 nodules from 3004 patients who underwent surgery. PTC (901 cases) was more frequent in solitary nodule (SN; 446/13 549, 3.3%) than in multinodular goiter (MNG; 411/19 923, 2%, chi(2)=48.8; P<0.0001), and in males (209/6382, 3.3%) than in females (648/26 945, 2.40%, chi(2)=15.58; P<0.0001). PTC prevalence in Graves' disease (GD; 13/286, 4.5%) and Hashimoto's thyroiditis (HT; 31/508, 6.1%) was higher than in SN, this difference being significant in HT (chi(2)=8.7; P=0.003), but not in GD (chi(2)=1.6; P=0.2). Using the multiple logistic regression analysis, independent risk predictors of PTC were determined, which were younger age (odds ratio (OR)=0.97, confidence interval (CI) 0.964-0.974; P<0.0001), male gender (OR=1.44, CI 1.231-1.683; P<0.0001), and SN versus MNG (OR=0.63, CI 0.547-0.717; P<0.0001). The individual risk predictivity was highly improved by including serum TSH in the prediction model, which was measured at FNA in 11 919 patients., Conclusion: A cytology suspicious or indicative of PTC was associated with younger age, male gender, and solitary versus multiple nodularity. These clinical parameters, together with serum TSH, may allow formulation of an algorithm that could be usefully applied to predict the risk of PTC in individual patients when cytology does not give a diagnostic result.

Background: Elastography is a newly developed dynamic technique that uses ultrasound (US) to provide an estimation of tissue stiffness by measuring the degree of distortion under the application of an external force. US elastography has been applied to differentiate malignant from benign lesions., Patients: This study included 92 consecutive patients with a single thyroid nodule who underwent surgery for compressive symptoms or suspicion of malignancy on fine needle aspiration cytology. Tissue stiffness on US elastography was scored from one (greatest elastic strain) to five (no strain)., Results: On US elastography: scores 1 and 2 were found in 49 cases, all benign lesions; score 3 in 13 cases, one carcinoma and 12 benign lesions; and scores 4 and 5 in 30 cases, all carcinomas. Thus, the elasticity scores 4-5 were highly predictive of malignancy (P < 0.0001), with a sensitivity of 97%, a specificity of 100%, a positive predictive value of 100%, and a negative predictive value of 98%. In 32 patients with an indeterminate fine needle aspiration result, the conventional US was not predictive of malignancy, while an US elastographic score of 4-5 was observed in six of seven (86%) patients with carcinoma on histology, and a score of 1-3 in all 25 patients with benign lesions., Conclusions: US elastography has great potential as an adjunctive tool for the diagnosis of thyroid cancer, especially in indeterminate nodules on cytology. Larger prospective studies are needed to confirm these results and establish the diagnostic accuracy of this new technique.

We describe a patient who survived an acute myocardial infarction caused by coronary embolization from a left ventricular papillary fibroelastoma. The tumour, which was detected by 2-D echocardiography, was successfully excised.