MR-guided cholecystostomy: Assessment of biplanar, real-time needle tracking in three pigs

Purpose: To demonstrate the feasibility of magnetic resonance (MR)-guided cholecystostomy using active, real-time, biplanar MR tracking in animal experiments. Methods: Experiments were performed on three fully anesthetized pigs in an interventional MR system (GE open). The gallbladder was displayed in two orthogonal planes using a heavily T2-weighted fast spin-echo sequence. These "cholangio roadmaps” were displayed on LCD monitors positioned in front of the interventionalist. A special coaxial MR-tracking needle, equipped with a small receive-only coil at its tip, was inserted percutaneously into the gallbladder under continuous, biplanar MR guidance. The MR-tracking sequence allowed sampling of the coil (needle tip) position every 120 msec. The position of the coil was projected onto the two orthogonal "cholangio roadmap” images. Results: Successful insertion of the needle was confirmed by aspiration of bile from the gallbladder. The process of aspiration and subsequent instillation of Gd-DTPA into the gallbladder was documented with fast gradient-recalled echo imaging. Conclusion: Biplanar, active, real-time MR tracking in combination with "cholangio roadmaps” allows for cholecystostomies in an interventional MRI environmen

Effect of aliskiren on post-discharge outcomes among diabetic and non-diabetic patients hospitalized for heart failure: insights from the ASTRONAUT trial

Aims The objective of the Aliskiren Trial on Acute Heart Failure Outcomes (ASTRONAUT) was to determine whether aliskiren, a direct renin inhibitor, would improve post-discharge outcomes in patients with hospitalization for heart failure (HHF) with reduced ejection fraction. Pre-specified subgroup analyses suggested potential heterogeneity in post-discharge outcomes with aliskiren in patients with and without baseline diabetes mellitus (DM). Methods and results ASTRONAUT included 953 patients without DM (aliskiren 489; placebo 464) and 662 patients with DM (aliskiren 319; placebo 343) (as reported by study investigators). Study endpoints included the first occurrence of cardiovascular death or HHF within 6 and 12 months, all-cause death within 6 and 12 months, and change from baseline in N-terminal pro-B-type natriuretic peptide (NT-proBNP) at 1, 6, and 12 months. Data regarding risk of hyperkalaemia, renal impairment, and hypotension, and changes in additional serum biomarkers were collected. The effect of aliskiren on cardiovascular death or HHF within 6 months (primary endpoint) did not significantly differ by baseline DM status (P = 0.08 for interaction), but reached statistical significance at 12 months (non-DM: HR: 0.80, 95% CI: 0.64-0.99; DM: HR: 1.16, 95% CI: 0.91-1.47; P = 0.03 for interaction). Risk of 12-month all-cause death with aliskiren significantly differed by the presence of baseline DM (non-DM: HR: 0.69, 95% CI: 0.50-0.94; DM: HR: 1.64, 95% CI: 1.15-2.33; P < 0.01 for interaction). Among non-diabetics, aliskiren significantly reduced NT-proBNP through 6 months and plasma troponin I and aldosterone through 12 months, as compared to placebo. Among diabetic patients, aliskiren reduced plasma troponin I and aldosterone relative to placebo through 1 month only. There was a trend towards differing risk of post-baseline potassium ≥6 mmol/L with aliskiren by underlying DM status (non-DM: HR: 1.17, 95% CI: 0.71-1.93; DM: HR: 2.39, 95% CI: 1.30-4.42; P = 0.07 for interaction). Conclusion This pre-specified subgroup analysis from the ASTRONAUT trial generates the hypothesis that the addition of aliskiren to standard HHF therapy in non-diabetic patients is generally well-tolerated and improves post-discharge outcomes and biomarker profiles. In contrast, diabetic patients receiving aliskiren appear to have worse post-discharge outcomes. Future prospective investigations are needed to confirm potential benefits of renin inhibition in a large cohort of HHF patients without D

MR-guided cholecystostomy: Assessment of biplanar, real-time needle tracking in three pigs

Purpose: To demonstrate the feasibility of magnetic resonance (MR)-guided cholecystostomy using active, real-time, biplanar MR tracking in animal experiments. Methods: Experiments were performed on three fully anesthetized pigs in an interventional MR system (GE open). The gallbladder was displayed in two orthogonal planes using a heavily T2-weighted fast spin-echo sequence. These "cholangio roadmaps” were displayed on LCD monitors positioned in front of the interventionalist. A special coaxial MR-tracking needle, equipped with a small receive-only coil at its tip, was inserted percutaneously into the gallbladder under continuous, biplanar MR guidance. The MR-tracking sequence allowed sampling of the coil (needle tip) position every 120 msec. The position of the coil was projected onto the two orthogonal "cholangio roadmap” images. Results: Successful insertion of the needle was confirmed by aspiration of bile from the gallbladder. The process of aspiration and subsequent instillation of Gd-DTPA into the gallbladder was documented with fast gradient-recalled echo imaging. Conclusion: Biplanar, active, real-time MR tracking in combination with "cholangio roadmaps” allows for cholecystostomies in an interventional MRI environmen

Preventing re-replication of chromosomal DNA

To ensure its faithful duplication, chromosomal DNA must be precisely duplicated in each cell cycle, with no sections left unreplicated and no sections replicated more than once. Eukaryotic cells achieve this by dividing replication into two non-overlapping phases. During late mitosis and G1, replication origins are ‘licensed’ for replication by loading the Mcm2-7 proteins to form a pre-replicative complex (pre-RC). Mcm2-7 proteins are then essential for initiating and elongating replication forks during S phase. Recent data have provided biochemical and structural insight into the process of replication licensing, and the mechanisms that regulate it during the cell cycle