In the largest real-world experience of novel agents in CLL, ibrutinib appears superior to idelalisib as first KI. Furthermore, in the setting of KI failure, alternate KI or venetoclax therapy appear superior to chemoimmunotherapy combinations. The use of venetoclax upon ibrutinib failure might be superior to idelalisib. These data support the need for trials testing sequencing strategies to optimize treatment algorithms.

Background The incidence and impact of clinical stroke and silent radiographic cerebral infarction complicating open surgical aortic valve replacement (AVR) are poorly characterized. Methods and Results We performed a prospective cohort study of subjects ≥ 65 years of age undergoing AVR for calcific aortic stenosis. Subjects were evaluated by neurologists pre-operatively and post-operatively, and underwent post-operative magnetic resonance imaging (MRI). Over a 4 year period, 196 subjects were enrolled at 2 sites. Mean age = 75.8 ± 6.2 years, 36% female, 6% non-white. Clinical strokes were detected in 17%, Transient Ischemic Attack in 2%, and in-hospital mortality was 5%. The frequency of stroke in the Society for Thoracic Surgery (STS) database in this cohort was 7%. Most strokes were mild; the median National Institutes of Health Stroke Scale (NIHSS) was 3 (interquartile range 1 – 9). Clinical stroke was associated with increased length of stay, median 12 vs 10 days, p = 0.02. Moderate or severe stroke (NIHSS ≥10) occurred in 8 (4%) and was strongly associated with in-hospital mortality, 38% vs 4%, p = 0.005. Of the 109 stroke-free subjects with post-operative MRI, silent infarct was identified in 59 (54%). Silent infarct was not associated with in-hospital mortality or increased length of stay. Conclusions Clinical stroke after AVR was more common than previously reported, more than double for this same cohort in the STS database, and silent cerebral infarctions were detected in over half of patients undergoing AVR. Clinical stroke complicating AVR is associated with increased length of stay and mortality.

Background Endothelial dysfunction present in patients with peripheral artery disease (PAD) may be better understood by measuring the temporal dynamics of blood flow and oxygen saturation during reactive hyperemia than by conventional static measurements. Methods and Results Perfusion, Intravascular Venous Oxygen saturation, and T2* (PIVOT), a recently developed MRI technique, was used to measure the response to an ischemia-reperfusion paradigm in ninety-six patients with PAD of varying severity, and ten healthy controls. Perfusion, venous oxygen saturation (SvO2), and T2* were each quantified in the calf at two second temporal resolution, yielding a dynamic time course for each variable. Compared to healthy controls, patients had a blunted and delayed hyperemic response. Moreover, patients with lower ankle-brachial index had: 1) a more delayed reactive hyperemia response time, manifesting as an increase in time to peak perfusion in the gastrocnemius, soleus, and peroneus muscles, and in the anterior compartment; 2) an increase in the time to peak T2* measured in the soleus muscle; and 3) a prolongation of the posterior tibial vein SvO2 washout time. Intra- and inter-session repeatability was also assessed. Results indicated that time to peak perfusion and time to peak T2* were the most reliable extracted time course metrics. Conclusions Perfusion, dynamic SvO2, and T2* response times following induced ischemia are highly correlated with PAD disease severity. Combined imaging of peripheral microvascular blood flow and dynamics of oxygen saturation with PIVOT may be a useful tool to investigate the pathophysiology of PAD.