The blood–brain barrier (BBB) severely limits the entry of systemically administered drugs including chemotherapy to the brain. In rodents, regadenoson activation of adenosine A2A receptors causes transient BBB disruption and increased drug concentrations in normal brain. This study was conducted to evaluate if activation of A2A receptors would increase intra-tumoral temozolomide concentrations in patients with glioblastoma. Patients scheduled for a clinically indicated surgery for recurrent glioblastoma were eligible. Microdialysis catheters (MDC) were placed intraoperatively, and the positions were documented radiographically. On post-operative day #1, patients received oral temozolomide (150 mg/m2). On day #2, 60 min after oral temozolomide, patients received one intravenous dose of regadenoson (0.4 mg). Blood and MDC samples were collected to determine temozolomide concentrations. Six patients were enrolled. Five patients had no complications from the MDC placement or regadenoson and had successful collection of blood and dialysate samples. The mean plasma AUC was 16.4 ± 1.4 h µg/ml for temozolomide alone and 16.6 ± 2.87 h µg/ml with addition of regadenoson. The mean dialysate AUC was 2.9 ± 1.2 h µg/ml with temozolomide alone and 3.0 ± 1.7 h µg/ml with regadenoson. The mean brain:plasma AUC ratio was 18.0 ± 7.8 and 19.1 ± 10.7% for temozolomide alone and with regadenoson respectively. Peak concentration and Tmax in brain were not significantly different. Although previously shown to be efficacious in rodents to increase varied size agents to cross the BBB, our data suggest that regadenoson does not increase temozolomide concentrations in brain. Further studies exploring alternative doses and schedules are needed; as transiently disrupting the BBB to facilitate drug entry is of critical importance in neuro-oncology.

Atherosclerotic cardiovascular disease (ASCVD) shares many risk factors with atrial fibrillation (AF). Obtaining computed tomography images of the pulmonary veins (CTPV) before AF ablation procedures is common and can incidentally detect coronary artery calcification (CAC). The purpose of this study was to investigate the prevalence of CAC on pre-ablation CTPV, the frequency of CAC reporting on CTPV reports, and its impact on statin therapy among patients hospitalized for AF procedures. We retrospectively evaluated consecutive patients undergoing CTPV and AF procedures from October 2016 to December 2017 in a single-center tertiary hospital. The patients’ demographic and clinical characteristics were analyzed. The CAC presence on CTPV was visually assessed. The severity was classified qualitatively. The statin therapy status was evaluated using the patient’s admission and discharge medication lists. A total of 638 subjects were included in our study, with 34.5% female. The mean age was 63.3 ± 10.8 years. CAC was detected in 70.1% of all patients, and in 58.1% of patients without a history of ASCVD. When present, CAC was documented in 92.6% of the clinical CTPV reports. While coronary artery atherosclerosis was present in a majority of AF patients, and its presence was widely reported, it was not associated with increased statin therapy at discharge.

Background: Left atrial volume (LAV) is an independent prognosticator of cardiovascular events. We investigated whether LAV could be accurately and reliably measured using coronary calcium score (CAC) scan. Methods: We retrospectively selected consecutive patients that underwent coronary CT angiography (CCTA) and CAC scans. A standardized approach to calculate LAV on images was implemented. The measurements of the LAV on CAC scans and CCTA were performed one to three weeks apart in a random fashion by two readers blinded to the results of each other. The LAV measurements from CAC scan were compared to those from CCTA using correlation analysis. Inter-observer and intra-observer agreement of LAV measurement using CAC scan was evaluated. Results: Final analysis included one hundred subjects, mean age 52 ± 12 years, 48% male. There was a trend of a marginally larger, albeit not clinically significant, mean LAV calculated using CAC scan compared to that using CCTA: 74.3 vs. 71.0 mL: p < 0.001; for reader 1, and 71.7 vs. 71.2 mL p = 0.06 for reader 2, respectively. LAV using CAC scan and CCTA were highly correlated (R = 0.954, p < 0.001 for reader1 and R = 0.945, p < 0.001 for reader 2). There was high reproducibility within each reader with ICC of 0.951 and 0.989 for readers 1 and 2, respectively (p < 0.001). Finally, there was high inter-observer agreement as indicated by R of 0.97 and ICC of 0.96 (p < 0.001 for both). Conclusions: Quantification of LAV from CAC scan using the proposed standardized approach is feasible, highly reliable and reproducible as compared to CCTA.