T-cell depletion facilitates reduced immunosuppression following organ transplantation and has been suggested to be pro-tolerant. However, the characteristics of post-depletional T cells have not been evaluated as they relate to tolerance induction. We therefore studied patients undergoing profound T-cell depletion with alemtuzumab or rabbit anti-thymocyte globulin following renal transplantation, evaluating the phenotype and functional characteristics of their residual cells. Naïve T cells and T cells with potential regulatory function (CD4+CD25+) were not prevalent following aggressive depletion. Rather, post-depletion T cells were of a single phenotype (CD3+CD4+CD45RA-CD62L-CCR7-) consistent with depletion-resistant effector memory T cells that expanded in the first month and were uniquely prevalent at the time of rejection. These cells were resistant to steroids, deoxyspergualin or sirolimus in vitro, but were calcineurin-inhibitor sensitive. These data demonstrate that therapeutic depletion begets a limited population of functional memory-like T cells that are easily suppressed with certain immunosuppressants, but cannot be considered uniquely pro-tolerant.

Key Points Question Can the diagnosis of benign disease or cancer in thyroid nodules with indeterminate cytology be established by molecular testing instead of diagnostic surgery? Findings This prospective, blinded, multicenter cohort study of a multigene genomic classifier (ThyroSeq v3) test included 257 indeterminate cytology thyroid nodules with informative test results. It demonstrated a high sensitivity (94%) and reasonably high specificity (82%), with 61% of the nodules yielding a negative test result and only 3% residual cancer risk in these nodules. Meanings Up to 61% of patients with indeterminate cytology thyroid nodules may avoid diagnostic surgery by undergoing multigene genomic classifier testing.

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Introduction: RAS mutations are common in thyroid tumors and confer a high risk of cancer when detected in fine-needle aspiration (FNA) specimens. Specific characteristics of RAS-positive thyroid cancers are not well described.

Introduction:Molecular testing of fine-needle aspiration (FNA) results helps diagnose thyroid cancer, although the additional cost of this adjunct has not been studied. We hypothesized that FNA molecular testing of two indeterminate categories (follicular lesion of undetermined significance and follicular/Hürthle cell neoplasm) can be cost saving.Methods:For a hypothetical group of euthyroid patients with a 1-cm or larger solitary thyroid nodule, a decision-tree model was constructed to compare the estimated costs of initial evaluation according to the current American Thyroid Association guidelines, either with molecular testing (MT) or without [standard of care (StC)]. Model endpoints were either benign FNA results or definitive histological diagnosis.Results:Molecular testing added $104 per patient to the overall cost of nodule evaluation (StC $578 vs. MT $682). In this distributed cost model, MT was associated with a decrease in the number of diagnostic lobectomies (9.7% vs. StC 11.6%), whereas initial total thyroidectomy was more frequent (18.2% vs. StC 16.1%). Although MT use added a diagnostic cost of $5031 to each additional indicated total thyroidectomy ($11,383), the cumulative cost was still less than the comparable cost of performing lobectomy ($7684) followed by completion thyroidectomy ($11,954) in the StC pathway, when indicated by histological results. In sensitivity analysis, savings were demonstrated if molecular testing cost was less than $870.Conclusions:Molecular testing of cytologically indeterminate FNA results is cost saving predominantly because of reduction in two-stage thyroidectomy. Appropriate use of emerging molecular testing techniques may thus help optimize patient care, improve resource use, and avoid unnecessary operation.

In a large consecutive series in which all ≥4 cm nodules had histology and were systematically evaluated by preoperative US and US-guided FNAB, the incidence of TC within the nodule was 22 %. The false negative rate of benign cytology was 10.4 %, and the absence of suspicious US features did not reliably exclude malignancy. At minimum, thyroid lobectomy should be strongly considered for all nodules ≥4 cm.

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