Скачать или смотреть Charité Clinical Journal Club (English) by Fred Luft - 18.09.2019

The N Engl J Med image of the week concerns a 60-year-old woman who presented to the emergency department with 2 months of blurry vision in her left eye. Her medical history was notable for breast cancer treated 3 years earlier with lumpectomy, axillary-node dissection, radiation, and hormonal therapy. Physical exam on upward gaze is demonstrated. What is the diagnosis? You are offered orbital metastasis, unilateral Graves ophthalmopathy, third-nerve palsy, orbital cellulitis, and idiopathic orbital inflammatory disease. The third nerve is compromised in any event. Roxadustat (FG-4592) is an oral inhibitor of hypoxia-inducible factor (HIF) prolyl hydroxylase that stimulates erythropoiesis and regulates iron metabolism. In phase 2 studies involving patients with chronic kidney disease, roxadustat increased levels of endogenous erythropoietin to within or near the physiologic range, along with increasing hemoglobin levels and improving iron homeostasis. Chinese investigators gave roxadustat to patients with chronic kidney disease not yet on dialysis (mean eGFR 15 ml/min). The primary efficacy analysis showed a significantly larger increase in the hemoglobin level from baseline over weeks 7 to 9 in the roxadustat group than in the placebo group (an increase of 1.9±1.2 g per deciliter vs. a decrease of 0.4±0.8 g per deciliter). Similarly, other hemoglobin end points, such as the percentage of patients who had a hemoglobin response (i.e., an increase of 1.0 g per deciliter from baseline) or who did not receive rescue therapy, were greater in the roxadustat group than in the placebo group. In spite of the robust erythropoiesis and the restriction of intravenous administration of iron in the roxadustat group, serum iron levels remained stable. Hepcidin levels decreased as will with roxadustat...