Teprotumumab per il trattamento dell'oftalmopatia basedowiana attiva

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Efficacia di selpercatinib nel trattamento dei carcinomi tiroidei con alterazione di RET: risultati di uno studio multicentrico open label, fase 1-2

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Hyponatremia and Cancer: From Bedside to Benchside

Hyponatremia is the most common electrolyte disorder encountered in hospitalized patients. This applies also to cancer patients. Multiple causes can lead to hyponatremia, but most frequently this electrolyte disorder is due to the syndrome of inappropriate antidiuresis. In cancer patients, this syndrome is mostly secondary to ectopic secretion of arginine vasopressin by tumoral cells. In addition, several chemotherapeutic drugs induce the release of arginine vasopressin by the hypothalamus. There is evidence that hyponatremia is associated to a more negative outcome in several pathologies, including cancer. Many studies have demonstrated that in different cancer types, both progression-free survival and overall survival are negatively affected by hyponatremia, whereas the correction of serum [Na+] has a positive effect on patient outcome. In vitro studies have shown that cells grown in low [Na+] have a greater proliferation rate and motility, due to a dysregulation in intracellular signalling pathways. Noteworthy, vasopressin receptors antagonists, which were approved more than a decade ago for the treatment of euvolemic and hypervolemic hyponatremia, have shown unexpected antiproliferative effects. Because of this property, vaptans were also approved for the treatment of polycystic kidney disease. In vitro evidence indicated that this family of drugs effectively counteracts proliferation and invasivity of cancer cells, thus possibly opening a new scenario among the pharmacological strategies to treat cancer

Impairment of Neurocognitive Functioning, Motor Performance, and Mood Stability in Hospitalized Patients With Euvolemic Moderate and Profound Hyponatremia

BACKGROUND: The impact of chronic moderate and profound hyponatremia on neurocognitive performance, motor skills, and mood stability has not been investigated systematically so far, and results regarding mild to moderate hyponatremia are inconsistent. Furthermore, it is not known whether treatment has an effect on outcome in these patients. METHODS: A total of 130 hospitalized patients with confirmed euvolemic hyponatremia (< 130 mEq/L) were subjected to a test battery (Mini-Mental State Examination, DemTect, Trail-Making Tests A and B, Beck Depression Inventory, Timed-up-and-go Test) before and after treatment; additionally, 50 normonatremic group-matched patients served as reference group. RESULTS: The scores of all tested domains were significantly worse in the hyponatremia group (median serum sodium [Na+] 122 (119-126) mEq/L) as compared to the reference group (P < 0.001), and the odds of obtaining a pathological test result increased markedly with more profound hyponatremic states (odds ratios between 5.0 and 21.8 in the group with Na+ <120 mEq/L compared to reference group). Inversely, treatment led to a significant amelioration of all test results with medium to large effect sizes. Linear regression models revealed the increment of Na+ as an important predictor of test outcome. CONCLUSION: We demonstrate a clear association between lower levels of Na+ beyond mild hyponatremia and impairment of neurocognitive and motor performance as well as mood disorders. Our analysis further suggests a causal role of hyponatremia in this context. However, there are apparent differences between the distinct tested domains warranting further investigations. (C) 2020 Elsevier Inc. All rights reserved

Moderate Hyponatremia Is Associated with Increased Risk of Mortality: Evidence from a Meta-Analysis

<div><p>Background</p><p>Hyponatremia is the most common electrolyte disorder in clinical practice, and evidence to date indicates that severe hyponatremia is associated with increased morbidity and mortality. The aim of our study was to perform a meta-analysis that included the published studies that compared mortality rates in subjects with or without hyponatremia of any degree.</p><p>Methods and Findings</p><p>An extensive Medline, Embase and Cochrane search was performed to retrieve the studies published up to October 1^st 2012, using the following words: “hyponatremia” and “mortality”. Eighty-one studies satisfied inclusion criteria encompassing a total of 850222 patients, of whom 17.4% were hyponatremic. The identification of relevant abstracts, the selection of studies and the subsequent data extraction were performed independently by two of the authors, and conflicts resolved by a third investigator. Across all 81 studies, hyponatremia was significantly associated with an increased risk of overall mortality (RR = 2.60[2.31–2.93]). Hyponatremia was also associated with an increased risk of mortality in patients with myocardial infarction (RR = 2.83[2.23–3.58]), heart failure (RR = 2.47[2.09–2.92]), cirrhosis (RR = 3.34[1.91–5.83]), pulmonary infections (RR = 2.49[1.44–4.30]), mixed diseases (RR = 2.59[1.97–3.40]), and in hospitalized patients (RR = 2.48[2.09–2.95]). A mean difference of serum [Na⁺] of 4.8 mmol/L was found in subjects who died compared to survivors (130.1±5.6 <i>vs</i> 134.9±5.1 mmol/L). A meta-regression analysis showed that the hyponatremia-related risk of overall mortality was inversely correlated with serum [Na⁺]. This association was confirmed in a multiple regression model after adjusting for age, gender, and diabetes mellitus as an associated morbidity.</p><p>Conclusions</p><p>This meta-analysis shows for the first time that even a moderate serum [Na⁺] decrease is associated with an increased risk of mortality in commonly observed clinical conditions across large numbers of patients.</p></div

Studies included in meta-analysis.

<p>H: patients with hyponatremia; NH: patients without hyponatremia; DM: diabetes mellitus; NA: not available.</p

Relation between serum [Na⁺] cut-off definition and overall mortality risk.

<p>Relation between serum [Na⁺] cut-off definition and overall mortality risk.</p

Trial flow diagram.

<p>Trial flow diagram.</p

Weighted differences (with 95% CI) of mean serum [Na⁺] in dead and alive patients.

<p>Weighted differences (with 95% CI) of mean serum [Na⁺] in dead and alive patients.</p

Odds ratio for overall mortality in patients with or without (no) hyponatremia according to the presence of myocardial infarction (A), heart failure (B), cirrhosis (C), pulmonary infection (D), mixed disease (E), or in hospitalized series of subjects (F).

<p>Odds ratio for overall mortality in patients with or without (no) hyponatremia according to the presence of myocardial infarction (A), heart failure (B), cirrhosis (C), pulmonary infection (D), mixed disease (E), or in hospitalized series of subjects (F).</p