Oesophageal Doppler and calibrated pulse contour analysis are not interchangeable within a goal-directed haemodynamic algorithm in major gynaecological surgery.

BACKGROUND: Evidence for the benefit of an intraoperative use of a goal-directed haemodynamic management has grown. We compared the oesophageal Doppler monitor (ODM, CardioQ-ODM™) with a calibrated pulse contour analysis (PCA, PiCCO2™) with regard to assessment of stroke volume (SV) changes after volume administration within a goal-directed haemodynamic algorithm during non-cardiac surgery. METHODS: The data were obtained prospectively in patients with metastatic ovarian carcinoma undergoing cytoreductive surgery. During surgery, fluid challenges were performed as indicated by the goal-directed haemodynamic algorithm guided by the ODM. Monitors were compared regarding precision and trending. Clinical characteristics associated with trending were studied by extended regression analysis. RESULTS: A total of 762 fluid challenges were performed in 41 patients resulting in 1524 paired measurements. The precision of ODM and PCA was 5.7% and 6.0% (P=0.80), respectively. Polar plot analysis revealed a poor trending between ODM and PCA with an angular bias of -7.1°, radial limits of agreement of -58.1° to 43.8°, and an angular concordance rate of 67.8%. Dose of norepinephrine (NE) (scaled 0.1 µg kg(-1) min(-1)) [adjusted odds ratio (OR) 0.606 (95% confidence interval, CI: 0.404-0.910); P=0.016] and changes in mean arterial pressure (MAP) to a fluid challenge (scaled 10%) [adjusted OR 0.733 (95% CI: 0.635-0.845); P<0.001] were associated with trending between ODM and PCA, whereas there was no relation to type of i.v. solution. CONCLUSIONS: Despite a similar precision, ODM and PCA were not interchangeable with regard to measuring SV changes within a goal-directed haemodynamic algorithm. A decrease in interchangeability coincided with increasing NE levels and greater changes of MAP to a fluid challenge.

Bortezomib inhibits human osteoclastogenesis.

In multiple myeloma, the overexpression of receptor activator of nuclear factor kappa B (NF-kappaB) ligand (RANKL) leads to the induction of NF-kappaB and activator protein-1 (AP-1)-related osteoclast activation and enhanced bone resorption. The purpose of this study was to examine the molecular and functional effects of proteasome inhibition in RANKL-induced osteoclastogenesis. Furthermore, we aimed to compare the outcome of proteasome versus selective NF-kappaB inhibition using bortezomib (PS-341) and I-kappaB kinase inhibitor PS-1145. Primary human osteoclasts were derived from CD14+ precursors in presence of RANKL and macrophage colony-stimulating factor (M-CSF). Both bortezomib and PS-1145 inhibited osteoclast differentiation in a dose- and time-dependent manner and furthermore, the bone resorption activity of osteoclasts. The mechanisms of action involved in early osteoclast differentiation were found to be related to the inhibition of p38 mitogen-activated protein kinase pathways, whereas the later phase of differentiation and activation occurred due to inhibition of p38, AP-1 and NF-kappaB activation. The AP-1 blockade contributed to significant reduction of osteoclastic vascular endothelial growth factor production. In conclusion, our data demonstrate that proteasomal inhibition should be considered as a novel therapeutic option of cancer-induced lytic bone disease.