Selecting answers with structured lexical expansion and discourse relations: LIMSI's participation at QA4MRE 2013

International audiencen this paper, we present the LIMSI’s participation to QA4MRE2013. We decided to test two kinds of methods. The first one focuses on complex questions, such as causal questions, and exploits discourse relations. Relation recognition shows promising results, however it has to be improved to have an impact on answer selection. The second method is based on semantic variations. We explored the English Wiktionary to find reformulations of words in the definitions, and used these reformulations to index the documents and select passages in the Entrance exams task

Intérêt d'un nouvel examen cytologique à au moins 5 ans d'intervalle dans le suivi des nodules thyroïdiens

ANGERS-BU Médecine-Pharmacie (490072105) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Endocrine side-effects of anti-cancer drugs: thyroid effects of tyrosine kinase inhibitors

International audienceTyrosine kinase inhibitors (TKIs) are currently used by most oncologists. Among their side effects, thyroid dysfunctions are nowadays clearly observed. Whereas changes in thyroid function tests have been originally described with sunitinib, we now know that many TKIs can induce hypothyroidism and hyperthyroidism. In this study, the various molecules implicated in thyroid dysfunctions are analysed and the latest data on physiopathological mechanisms are approached in order to propose a strategy of thyroid monitoring of patients on TKI therapy.</p

Somatostatin receptor ligands induce TSH deficiency in thyrotropin-secreting pituitary adenoma

International audienc

Familial Dysalbuminemic Hyperthyroxinemia: An Underdiagnosed Entity

Resistance to thyroid hormone (RTH) is a syndrome characterized by impaired sensitivity of tissues to thyroid hormone (TH). The alteration of TH-binding proteins, such as in Familial Dysalbuminemic Hyperthyroxinemia (FDH), can mimic the abnormal serum thyroid tests typical of RTH. We aimed to characterize a population referred to our center with suspected RTH and estimate the proportion of patients with FDH. For 303 different families, we collected clinical and hormonal data and sequenced the thyroid hormone receptor &beta; gene (THRB) and exon 7 of the albumin gene (ALB). We found 56 THRB variants (i.e., 38% of the 303 index cases, called RTH&beta; group). Among the samples screened for FDH variants, 18% had the variant R218H in ALB (FDH group); in addition, 71% of the cases had neither variant (non-FDH/RTH&beta; group). Patients with FDH had significantly lower free T3 (fT3) and free T4 (fT4) levels and more often an isolated elevation of fT4 than RTH&beta; patients. Clinically, patients with FDH had fewer symptoms than patients with RTH&beta;. Our study suggests that FDH should be systematically considered when examining patients suspected of having RTH. In most cases, they present no clinical symptoms, and their biochemical alterations show an elevation of fT4 levels, while fT3 levels are 1.11 times below the upper limit of the assay

Clinically Symptomatic Resistance to Thyroid Hormone β Syndrome Because of THRB Gene Mosaicism

International audienceAbstract Context Resistance to thyroid hormone β syndrome (RTHβ) is caused by pathogenic variants in the THRB gene, but such variants are found in only 85% of cases. We report the case of a patient with RTHβ phenotype but for whom we found a pathogenic variant of the THRB gene in a mosaic state. Case Description The patient is a 52-year-old woman with clinical and biological signs of RTHβ. Symptoms included asthenia, cardiac palpitations, and diarrhea. Repeated thyroid function tests showed an elevated serum TSH, elevated serum free T4, and variably normal or slightly elevated serum fT3. Pituitary magnetic resonance imaging was normal, and the thyrotropin-releasing hormone test result was compatible with the diagnosis of RTHβ syndrome. Initial Sanger sequencing on blood samples could not highlight the presence of a mosaic variant because of insufficient sensitivity. When next-generation sequencing became accessible, blood samples were retested and we found a known pathogenic variant: c.949G &gt; A; p.(ala317Thr), with an allelic frequency of 12%. Other samples from tissues of different embryological origin were also tested and found an allelic frequency of 5.7%, 17.9%, 9.9%, 6.4%, and 0% on urine tests, oral swab, nasal mucosa swab, skin biopsy, and conjunctival swab, respectively. Cloning confirmed the allelic frequency observed. Conclusions We highlight that a pathogenic variant in a mosaic state in the THRB gene may be the cause of an authentic RTHβ syndrome. High-throughput sequencing of multiple tissues eases the detection of pathogenic variant in a mosaic state and allows the correct diagnosis of patients with true RTHβ, thus avoiding patient mismanagement

AZP-531, an unacylated ghrelin analog, improves food-related behavior in patients with Prader-Willi syndrome: A randomized placebo-controlled trial

<div><p>Context and objective</p><p>Prader-Willi syndrome (PWS) is characterized by early-onset hyperphagia and increased circulating levels of the orexigenic Acylated Ghrelin (AG) hormone with a relative deficit of Unacylated Ghrelin (UAG). AZP-531, a first-in-class UAG analog, was shown to inhibit the orexigenic effect of AG in animals, to improve glycemic control and decrease body weight in humans. We aimed to investigate the safety and efficacy of AZP-531 in patients with PWS for whom no approved treatment for hyperphagia is currently available.</p><p>Methods and design</p><p>Multi-center, randomized, double-blind, placebo-controlled trial. Forty-seven patients with genetically confirmed PWS and evidence of hyperphagia received daily subcutaneous injections of AZP-531 (3 and 4 mg for 50–70 kg and >70 kg body weight, respectively) or matching placebo for 14 days. Assessments included adverse events, vital signs, safety laboratory tests, the Hyperphagia Questionnaire (HQ), patient-reported appetite, body composition and glycemic measures.</p><p>Results</p><p>AZP-531 was well tolerated. There was a significant improvement with AZP-531 versus placebo in the mean total score, the 9-item score and the severity domain score of the HQ (p < .05). The highest reduction in the total and 9-item scores was observed in AZP-531 subjects with the highest hyperphagia score at baseline. Findings were supported by a reduction in appetite scores observed with AZP-531 only. Body weight did not change in both groups while a significant reduction in waist circumference and fat mass was observed only with AZP-531. AZP-531 significantly decreased post-prandial glucose levels in a baseline glucose dependent fashion.</p><p>Conclusions</p><p>AZP-531 may constitute a new treatment strategy to improve hyperphagia and metabolic issues in patients with PWS. These findings support further investigation in longer-term clinical trials.</p></div

Endocrine side-effects of new anticancer therapies: Overall monitoring and conclusions

IF 0.795 (2017)International audienceThe present final consensus statement of the French Society of Endocrinology lays out the assessments that are to be systematically performed before and during anticancer treatment by immunotherapy, tyrosine kinase inhibitors or mTOR inhibitors, even without onset of any endocrinopathy. It also discusses the CTCAE adverse event grading system in oncology and the difficulty of implementing it for endocrine side-effects of these anticancer treatments. Notably, this is why certain treatment steps applied in other side-effects (e.g., high-dose corticosteroids, contraindications to immunotherapy, etc.) need to be discussed before implementation for endocrine side-effects