👤 Ramya Thota

Despite the growing burden of youth-onset type 2 diabetes (Y-T2D), the long-term risk for fatal/non-fatal cardiovascular disease (CVD) in Y-T2D compared to peers is unknown. The International Childhood Cardiovascular Cohort (i3C) combined-risk z-score is a novel tool for predicting 35-year risk of adult CVD events. In Y-T2D compared to peers (Lean and overweight/obesity [OW/OB]), we estimated predicted CVD events and evaluated the relationship of the i3C z-score with risk-enhancing factors. In a pooled cohort cross-sectional analysis of 1547 adolescents and young adults (AYA) aged 10-25 years [627 Lean, 803 OW/OB, 117 Y-T2D], i3C combined-risk z-scores and estimated hazard ratios (HR) were obtained from the published i3C equation using risk z-scores of systolic blood pressure, body mass index (BMI), smoking history, total cholesterol, and triglycerides. ANCOVA regression models were used: 1) to compare i3C z-scores and HR in AYA with Y-T2D, OW/OB and Lean peers, and 2) to measure associations between i3C estimated HR and risk-enhancing factors including apolipoprotein B (ApoB), total low density lipoprotein particle number (LDL-P), and high sensitivity C reactive protein (hsCRP). Models were adjusted for diagnosis group, race, study center and multiple comparisons with Bonferroni. Y-T2D had the highest i3C z-score (Y-T2D: 1.23 [1.10, 1.36] vs. OW/OB: 0.84 [0.80, 0.88] vs. Lean: -0.11 [-0.15, -0.06], mean[95%CI]) and estimated HR for predicted CVD events (Y-T2D: 4.25 [3.65-4.86] vs. OW/OB: 3.04 [2.85-3.22] vs. Lean: 0.95 [0.74-1.17], HR [95% CI]). Risk-enhancing factors increased the HR for predicted CVD risk by 0.3 for each 10 mg/dL increase in ApoB, 0.1 for each 100 nmol/L increase in LDL-P, and 0.16 for each 2 mg/L increase in hsCRP, all P < 0.001. Y-T2D had an estimated 4.5- and 1.4-times higher risk for predicted CVD events compared to Lean and OW/OB peers, respectively. Lipoprotein and inflammatory risk-enhancing factors may help stratify and guide primary prevention strategies in high-risk AYA. Show less

The Targeted Agent and Profiling Utilization Registry Study is a phase II basket trial evaluating the antitumor activity of commercially available targeted agents in patients with advanced cancer and genomic alterations known to be drug targets. Results from cohorts of patients with metastatic breast cancer (BC) with Eligible patients had measurable disease, Eastern Cooperative Oncology Group performance status 0-2, adequate organ function, and no standard treatment options. Simon's two-stage design was used with a primary end point of disease control (DC), defined as objective response (OR) or stable disease of at least 16 weeks duration (SD16+) according to RECIST v1.1. Secondary end points included OR, progression-free survival, overall survival, duration of response, duration of stable disease, and safety. Forty patients with BC with Sunitinib did not meet prespecified criteria to declare a signal of antitumor activity in patients with BC with either Show less