New treatments directly targeting polymerization of sickle hemoglobin (HbS), the proximate event in the pathophysiology of sickle cell disease (SCD), are needed to address the severe morbidity and early mortality associated with the disease. Voxelotor (GBT440) is a first-in-class oral therapy specifically developed to treat SCD by modulating the affinity of hemoglobin (Hb) for oxygen, thus inhibiting HbS polymerization and downstream adverse effects of hemolytic anemia and vaso-occlusion. GBT440-001 was a phase 1/2 randomized, double-blind, placebo-controlled, single and multiple ascending dose study of voxelotor in adult healthy volunteers and patients with SCD, followed by a single-arm, open-label extension study. This report describes results of voxelotor (500-1000 mg per day) in patients with sickle cell anemia. The study evaluated the safety, tolerability, pharmacokinetic, and pharmacodynamic properties of voxelotor and established proof of concept by improving clinical measures of anemia, hemolysis, and sickling. Thirty-eight patients with SCD received 28 days of voxelotor 500, 700, or 1000 mg per day or placebo; 16 patients received 90 days of voxelotor 700 or 900 mg per day or placebo. Four patients from the 90-day cohort were subsequently enrolled in an extension study and treated with voxelotor 900 mg per day for 6 months. All patients who received multiple doses of voxelotor for ≥28 days experienced hematologic improvements including increased Hb and reduction in hemolysis and percentage of sickled red cells, supporting the potential of voxelotor to serve as a disease-modifying therapy for SCD. Voxelotor was well tolerated with no treatment-related serious adverse events and no evidence of tissue hypoxia. These trials were registered at www.clinicaltrials.gov as #NCT02285088 and #NCT03041909.

• The CHAMPION-1 study is the first clinical trial to investigate carfilzomib on a once-weekly dosing schedule with dexamethasone.• Once-weekly carfilzomib (30-minute infusion; 20 and 70 mg/m 2 ) with dexamethasone is feasible and effective in relapsed/refractory MM. , the most common grade ‡3 adverse events were fatigue (11%) and hypertension (7%). Overall response rate at 70 mg/m 2 was 77%. Median progression-free survival was 12.6 months. These findings merit additional evaluation of the once-weekly dosing regimen. This trial was registered at www.clinicaltrials. gov as #NCT01677858. (Blood. 2016;127(26):3360-3368)

Background: Sickle cell disease (SCD) is a devastating, multisystemic disorder that affects millions of people worldwide. The earliest clinical manifestations of SCD can affect infants as young as 6 months of age, and pediatric patients are at risk for acute and life-threatening complications. Early intervention with treatments that target the underlying pathophysiological mechanism of SCD, sickle hemoglobin (HbS) polymerization, are expected to slow disease progression and circumvent disease-associated morbidity and mortality. Procedure: The HOPE-KIDS 1 trial (NCT02850406) is an ongoing four-part, phase 2a, open-label, single-and multiple-dose study to evaluate the pharmacokinetics, efficacy, and safety of voxelotor-a first-in-class HbS polymerization inhibitor-in patients aged 6 months to 17 years with SCD. Initial findings from a cohort of 45 patients aged 4 to 11 years who received voxelotor treatment for up to 48 weeks are reported.Results: Hemoglobin (Hb) response, defined as a >1.0 g/dl increase from baseline, was achieved at week 24 by 47% (n = 16/34) of patients with Hb measurements at baseline and week 24. At week 24, 35% (n = 12/34) and 21% (n = 7/34) of patients had a >1.5 g/dl increase and a >2.0 g/dl increase from baseline in Hb concentration, respectively. Concurrent improvements in hemolytic markers were observed.

Postoperative complications following curative lung cancer surgery are well recognised, but there is limited data on 30-day readmission rates. The UK Thoracic Surgery Group conducted a multicentre review over a 3-month period to assess readmission rates. Overall readmission among the 268 patients who had undergone primary lung cancer surgery was 30 (11%); 14/30 of readmissions occurred within 7 days of discharge, with 13/30 patients readmitted to a hospital that had not performed the surgery. The causes of readmission were mainly pulmonary related (16/30). Readmission was associated with being discharged with a pleural drain 11/30 (P<0.01), having two or more postoperative complications 11/30 (P<0.01) and a patient's readiness for discharge 9/30 (P=0.001). There was a trend toward an association with smoking 13/30 (P=0.18). The authors suggest that a greater focus on patients presenting with characteristics associated with readmission, and incorporating a patient's readiness for discharge, may reduce readmission, although more studies are needed.