1,721,018 research outputs found

    Targeting the right population for T3 + T4 combined therapy: where are we now and where to next?

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    The universal applicability of levothyroxine (LT4) monotherapy for the treatment of hypothyroidism has been questioned in recent years. Indeed, it is now clear that about 10–15% of LT4-treated hypothyroid patients are dissatisfied with their treatment. It is plausible that this subset of hypothyroid patients may need T3 + T4 combined therapy to restore peripheral euthyroidism. To address this issue, many clinical trials have investigated the effect of T3 + T4 combinations versus standard LT4-based therapy. However, to date, results have been inconclusive, mainly due to the lack of markers that identify candidates for combination therapy. A breakthrough in this field came with the recent finding that several single-nucleotide polymorphisms in the deiodinase genes are associated with the persistence of hypothyroid symptoms in biochemically euthyroid LT4-treated patients, and are thus markers of candidates for combination therapy. In addition, whole-genome association studies are expanding our knowledge of other genes of the thyroid hormone (TH) pathway that affect serum TH levels. To target the right population for the T3 + T4 combined therapy, the next step is to translate these new findings into prospective trials. Hopefully, this will pave the way to personalized therapy for each hypothyroid patient

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Management of one patient with oligoprogressive thyroid cancer during treatment with lenvatinib

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    Recent thyroid cancer guidelines found it reasonable to use local therapies during treatment with tyrosine kinase inhibitors (TKIs) in selected patients with oligoprogressive disease, namely, in the presence of a single progressing lesion in an otherwise TKI-responsive metastatic cancer. However, there is a lack of experience in the management of oligoprogressive thyroid cancers. This report illustrates the case of one patient with oligoprogressive thyroid cancer during therapy with lenvatinib. We found that the application of local ablative therapy in oligoprogressive disease prolonged the progression-free survival and thus extended the time to therapy interruption. However, the optimal care for TKI-treated oligoprogressive cancers remains unclear and needs to be investigated in prospective trials

    Local ablative therapy of oligoprogressive TKI-treated thyroid cancer

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    Metastatic cancer patients generally respond well to treatment with tyrosine kinase inhibitors (TKIs). However, TKI resistance occurs in almost all cases and often leads to a change in treatment. Recent guidelines, including thyroid cancer, raised the possibility of locally treating TKI-resistant oligoprogressive disease, i.e., one or a few progressing lesions in an otherwise treatment-responsive metastatic cancer, thereby obviating the need to change the ongoing TKI. To determine the benefits of this intervention, we reviewed studies on the use of LAT for TKI-treated oligoprogressive cancers. We found that in non-small cell lung cancer at least, LAT prolongs disease control and the duration of exposure to a TKI irrespective of the LAT used. Moreover, we reviewed the local ablative therapies (LATs) that are feasible for the local control of oligoprogressive thyroid cancer. Lastly, we report two illustrative cases of patients with oligoprogressive thyroid cancer treated with two different LATs while on therapy with TKIs. Both LATs extended the duration of disease control and the time of exposure to the ongoing TKI, thereby indicating that LAT is a favorable option for TKI-treated oligoprogressive thyroid cancer. Prospective randomized studies are needed to verify the benefit of LATs in terms of progression-free and overall survival in this increasingly frequent clinical setting

    Variations on the Author

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    “Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship

    Appropriate Similarity Measures for Author Cocitation Analysis

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    We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis

    Treatment of Cushing disease: overview and recent findings

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    Tatiana Mancini1, Teresa Porcelli2, Andrea Giustina21Department of Internal Medicine and Medical Specialties, San Marino Hospital, San Marino, Republic of San Marino, 2Department of Medical and Surgical Sciences, University of Brescia, Brescia, ItalyAbstract: Endogenous Cushing syndrome is an endocrine disease caused by excessive secretion of adrenocorticotropin hormone in approximately 80% of cases, usually by a pituitary corticotroph adenoma (Cushing disease [CD]). It is a heterogeneous disorder requiring a multidisciplinary and individualized approach to patient management. The goals of treatment of CD include the reversal of clinical features, the normalization of biochemical changes with minimal morbidity, and long-term control without recurrence. Generally, the treatment of choice is the surgical removal of the pituitary tumor by transsphenoidal approach, performed by an experienced surgeon. Considering the high recurrence rate, other treatments should be considered. Second-line treatments include more radical surgery, radiation therapy, medical therapy, and bilateral adrenalectomy. Drug treatment has been targeted at the hypothalamic or pituitary level, at the adrenal gland, and also at the glucocorticoid receptor level. Frequently, medical therapy is performed before surgery to reduce the complications of the procedure, reducing the effects of severe hypercortisolism. Commonly, in patients in whom surgery has failed, medical management is often essential to reduce or normalize the hypercortisolemia, and should be attempted before bilateral adrenalectomy is considered. Medical therapy can be also useful in patients with CD while waiting for pituitary radiotherapy to take effect, which can take up to 10 years or more. So far, results of medical treatment of CD have not been particularly relevant; however, newer tools promise to change this scenario. The aim of this review is to analyze the results and experiences with old and new medical treatments of CD and to reevaluate medical therapies for complications of CD and hypopituitarism in patients with cured CD.Keywords: ketoconazole, somatostatin analogs, dopamine agonists, rosiglitazone, Cushing disease, glucocorticoids, hypopituitaris
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