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Background: Patients with moderate to severe hypothyroidism and mainly patients with myxedema may exhibit reduced sodium levels (<135 mmol/L). Summary: The aim of this short review is the presentation of the mechanisms of hyponatremia and of the available data regarding its implications and treatment in patients with hypothyroidism. Hypothyroidism is one of the causes of hyponatremia, thus thyroid-stimulating hormone determination is mandatory during the evaluation of patients with reduced serum sodium levels. The main mechanism for the development of hyponatremia in patients with chronic hypothyroidism is the decreased capacity of free water excretion due to elevated antidiuretic hormone levels, which are mainly attributed to the hypothyroidism-induced decrease in cardiac output. However, recent data suggest that the hypothyroidism-induced hyponatremia is rather rare and probably occurs only in severe hypothyroidism and myxedema. Other possible causes and superimposed factors of hyponatremia (e.g. drugs, infections, adrenal insufficiency) should be considered in patients with mild/moderate hypothyroidism. Treatment of hypothyroidism and fluid restriction are usually adequate for the management of mild hyponatremia in patients with hypothyroidism. Patients with possible hyponatremic encephalopathy should be urgently treated according to current guidelines. Conclusions: Severe hypothyroidism may be the cause of hyponatremia. All hypothyroid patients with low serum sodium levels should be evaluated for other causes and superimposed factors of hyponatremia and treated accordingly.

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Background Acute respiratory distress syndrome and cytokine release syndrome are the major complications of coronavirus disease 2019 (COVID-19) associated with increased mortality risk. Objectives We performed a meta-analysis to assess the efficacy and safety of anakinra in adult hospitalized non-intubated patients with COVID-19. Search methods Relevant trials were identified by searching literature until 24 April 2021 using the following terms: anakinra, interleukin 1, coronavirus, COVID-19, SARS-CoV-2. Selection criteria Trials evaluating the effect of anakinra on the need for invasive mechanical ventilation and mortality in hospitalized non-intubated patients with COVID-19. Results Nine studies (n = 1,119) were eligible for inclusion in the present meta-analysis. Their bias risk with reference to the assessed parameters was high. In pooled analyses, anakinra reduced the need for invasive mechanical ventilation (odds ratio, OR: 0·38, 95% confidence interval, CI: 0·17–0·85, p= 0.02, I2=67%; 6 studies, n = 587) and mortality risk (OR: 0·32, 95% CI: 0·23–0·45, p&lt; 0·00001, I2=0%; 9 studies, n = 1,119) compared with standard of care therapy. There were no differences regarding the risk of adverse events, including liver dysfunction (OR: 0·75, 95% CI: 0·48–1·16, p&gt; 0·05, I2=28%; 5 studies, n = 591) and bacteremia (OR: 1·07, 95% CI: 0·42–2·73, p&gt; 0·05, I2=71%; 6 studies, n = 727). Conclusions Available evidence shows that treatment with anakinra reduces both the need for invasive mechanical ventilation and mortality risk of hospitalized non-intubated patients with COVID-19 without increasing the risk of adverse events. Confirmation of efficacy and safety requires randomized placebo-controlled trials.

Hyponatremia (Na(+) <135 mmol/l) is the most common electrolyte disorder. Cirrhosis represents a rather frequent cause of hyponatremia mainly due to systemic and splanchnic vasodilation resulting in decreased effective arterial blood volume, which leads to excessive non-osmotic secretion of antidiuretic hormone. However, hyponatremia of multifactorial origin may be seen in patients with liver diseases. The review focuses on the factors and pathogenetic mechanisms of decreased sodium levels other than the hemodynamic compromise of cirrhosis in patients with liver diseases. The mechanisms and causal or contributing role of pseudohyponatremia, hyperglycemia, infections, drugs and toxins as well as of endocrine disorders, renal failure and cardiac disease in patients with liver disease are meticulously discussed. Hyponatremia of multifactorial origin is frequently observed in patients with liver diseases, and special efforts should be made to delineate the underlying causative and precipitating factors as well as the risk factors of the osmotic demyelination syndrome in order to properly manage this serious electrolyte disorder and avoid treatment pitfalls.

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Complement C3 activation contributes to COVID-19 pathology, and C3 targeting has emerged as a promising therapeutic strategy. We provide interim data from ITHACA, the first randomized trial evaluating a C3 inhibitor, AMY-101, in severe COVID-19 (PaO2/FiO2 ≤ 300 mmHg). Patients received AMY-101 ( n = 16) or placebo ( n = 15) in addition to standard of care. AMY-101 was safe and well tolerated. Compared to placebo (8 of 15, 53.3%), a higher, albeit nonsignificant, proportion of AMY-101–treated patients (13 of 16, 81.3%) were free of supplemental oxygen at day 14. Three nonresponders and two placebo-treated patients succumbed to disease-related complications. AMY-101 significantly reduced CRP and ferritin and restrained thrombin and NET generation. Complete and sustained C3 inhibition was observed in all responders. Residual C3 activity in the three nonresponders suggested the presence of a convertase-independent C3 activation pathway overriding the drug’s inhibitory activity. These findings support the design of larger trials exploring the potential of C3-based inhibition in COVID-19 or other complement-mediated diseases.

The calculation of osmolal gap is crucial in the differential diagnosis of many patients presenting in emergency departments with possible drug or substance overdose as well as in comatose hospitalized patients.