Therapeutic augmentation of NO-sGC-cGMP signalling: lessons learned from pulmonary arterial hypertension and heart failure

Heart Failure Reviews - The nitric oxide (NO)–guanylate cyclase (GC)–cyclic guanosine monophosphate (cGMP) pathway plays an important role in cardiovascular, pulmonary and renal...     

Patient preferences and predicted relative uptake for targeted therapies in metastatic colorectal cancer: a discrete choice experiment

Abstract

Objective

Ras wild-type metastatic colorectal cancers (mCRC) may be treated with anti-vascular endothelial growth factor (VEGF) or anti-epidermal growth factor receptor (EGFR) agents. We aim to estimate patients’ preferences for mCRC treatment and relative importance of cost, efficacy improvement, avoidance of side effects and therapy convenience, and relative uptake between profiles that resemble Bevacizumab (anti-VEGF) and Cetuximab (anti-EGFR), two commonly prescribed mCRC targeted therapies.     

Heat Sink Effect on Tumor Ablation Characteristics as Observed in Monopolar Radiofrequency,Bipolar Radiofrequency,and Microwave,Using Ex Vivo Calf Liver Model

Thermal ablation of liver tumors near large blood vessels is affected by the cooling effect of blood flow, leading to incomplete ablation. Hence, we conducted a comparative investigation of heat sink effect in monopolar (MP) and bipolar (BP) radiofrequency ablation (RFA), and microwave (MW) ablation devices.With a perfused calf liver, the ablative performances (volume, mass, density, dimensions), with and without heat sink, were measured. Heat sink was present when the ablative tip of the probes were 8.0 mm close to a major hepatic vein and absent when >30 mm away. Temperatures (T1 and T2) on either side of the hepatic vein near the tip of the probes, heating probe temperature (T3), outlet perfusate temperature (T4), and ablation time were monitored.With or without heat sink, BP radiofrequency ablated a larger volume and mass, compared with MP RFA or MW ablation, with latter device producing the highest density of tissue ablated. MW ablation produced an ellipsoidal shape while radiofrequency devices produced spheres.Percentage heat sink effect in Bipolar radiofrequency : Mono-polar radiofrequency : Microwave was (Volume) 33:41:22; (mass) 23:56:34; (density) 9.0:26:18; and (relative elipscity) 5.8:12.9:1.3, indicating that BP and MW devices were less affected.Percentage heat sink effect on time (minutes) to reach maximum temperature (W) = 13.28:9.2:29.8; time at maximum temperature (X) is 87:66:16.66; temperature difference (Y) between the thermal probes (T3) and the temperature (T1 + T2)/2 on either side of the hepatic vessel was 100:87:20; and temperature difference between the (T1 + T2)/2 and temperature of outlet circulating solution (T4), Z was 20.33:30.23:37.5.MW and BP radiofrequencies were less affected by heat sink while MP RFA was the most affected. With a single ablation, BP radiofrequency ablated a larger volume and mass regardless of heat sink.