Current treatment of anemia in chronic kidney disease (CKD) with erythropoiesis-stimulating agents can lead to substantial hemoglobin oscillations above target range and high levels of circulating erythropoietin. Vadadustat (AKB-6548), a novel, titratable, oral hypoxia-inducible factor prolyl hydroxylase inhibitor induces endogenous erythropoietin synthesis and enhances iron mobilization. In this 20-week, double-blind, randomized, placebo-controlled, phase 2b study, we evaluated the efficacy and safety of once-daily vadadustat in patients with stages 3a to 5 non-dialysis-dependent CKD. The primary endpoint was the percentage of patients who, during the last 2 weeks of treatment, achieved or maintained either a mean hemoglobin level of 11.0 g/dl or more or a mean increase in hemoglobin of 1.2 g/dl or more over the predose average. Significantly, the primary endpoint was met in 54.9% of patients on vadadustat and 10.3% of patients on placebo. Significant increases in both reticulocytes and total iron-binding capacity and significant decreases in both serum hepcidin and ferritin levels were observed in patients on vadadustat compared with placebo. The overall incidence of adverse events was comparable between the 2 groups. Serious adverse events occurred in 23.9% and 15.3% of the vadadustat- and placebo-treated patients, respectively. Three deaths occurred in the vadadustat arm. Thus, this phase 2b study demonstrated that vadadustat raised and maintained hemoglobin levels in a predictable and controlled manner while enhancing iron mobilization in patients with nondialysis-dependent CKD.

Linezolid demonstrated efficacy and similar safety outcomes equivalent to those for vancomycin in febrile neutropenic patients with cancer.

The detrimental effects of both diabetes mellitus (DM) and hyperglycemia in the perioperative period are well established and have driven extensive efforts to control blood glucose concentration (BGC) in a variety of clinical settings. It is now appreciated that acute BGC spikes, hypoglycemia, and high glycemic variability (GV) lead to more endothelial dysfunction and oxidative stress than uncomplicated, chronically elevated BGC. In the perioperative setting, fasting is the primary approach to reducing the risk for pulmonary aspiration; however, prolonged fasting drives the body into a catabolic state and therefore may increase GV. Elevated GV in the perioperative period is associated with an increased risk for postoperative complications, including morbidity and mortality. These challenges pose a conundrum for the management of patients typically instructed to fast for at least 8 h before surgery. Preliminary evidence suggests that the administration of an oral preoperative carbohydrate load (PCL) to stimulate endogenous insulin production and reduce GV in the perioperative period may attenuate BGC spikes and ultimately decrease postoperative morbidity, without significantly increasing the risk of pulmonary aspiration. The aim of this scoping review is to summarize the available evidence on the impact of PCL on perioperative GV and surgical outcomes, with an emphasis on evidence pertaining to patients with DM. The clinical relevance of GV will be summarized, the relationship between GV and postoperative course will be explored, and the impact of PCL on GV and surgical outcomes will be presented. A total of 13 articles, presented in three sections, were chosen for inclusion. This scoping review concludes that the benefits of a PCL outweigh the risks in most patients, even in those with well controlled type 2 DM. The administration of a PCL might effectively minimize metabolic derangements such as GV and ultimately result in reduced postoperative morbidity and mortality, but this remains to be proven. Future efforts to standardize the content and timing of a PCL are needed. Ultimately, a rigorous data-driven consensus opinion regarding PCL administration that identifies optimal carbohydrate content, volume, and timing of ingestion should be established.

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