The success of sorafenib in prolonging survival of patients with hepatocellular carcinoma (HCC) makes therapeutic inhibition of angiogenesis a component of treatment for HCC. To enhance therapeutic efficacy, overcome drug resistance and reduce toxicity, combination of antiangiogenic agents with chemotherapy, radiotherapy or other targeted agents were evaluated. Nevertheless, the use of antiangiogenic therapy remains suboptimal regarding dosage, schedule and duration of therapy. The issue is further complicated by combination antiangiogenesis to other cytotoxic or biologic agents. There is no way to determine which patients are most likely respond to a given form of antiangiogenic therapy. Activation of alternative pathways associated with disease progression in patients undergoing antiangiogenic therapy has also been recognized. There is increasing importance in identifying, validating and standardizing potential response biomarkers for antiangiogenesis therapy for HCC patients. In this review, biomarkers for antiangiogenesis therapy including systemic, circulating, tissue and imaging ones are summarized. The strength and deficit of circulating and imaging biomarkers were further demonstrated by a series of studies in HCC patients receiving radiotherapy with or without thalidomide. 相似文献
The inflammatory response induced by cardiopulmonary bypass decreases vascular tone, which in turn can lead to vasoplegic syndrome. Indeed the hypotension consequent to on-pump cardiac surgery often necessitates vasopressor and intravenous fluid support. Methylene blue counteracts vasoplegic syndrome by inhibiting the formation of nitric oxide.We report the use of methylene blue in a 75-year-old man who developed vasoplegic syndrome after cardiac surgery. After the administration of methylene blue, his hypotension improved to the extent that he could be weaned from vasopressors. The use of methylene blue should be considered in patients who develop hypotension refractory to standard treatment after cardiac surgery. 相似文献
Introduction: Pharmacological options to address the imbalance between bone resorption and accrual in osteoporosis include anti-resorptive and osteoanabolic agents. Unique biologic pathways such as the Wnt/β-catenin pathway have been targeted in the quest for new emerging therapeutic strategies.
Areas covered: This review provides an overview of existing pharmacotherapy for osteoporosis in women and explore state-of–the-art and emerging therapies to prevent bone loss, with an emphasis on the mechanism of action, indications and side effects.
Expert opinion: Bisphosphonates appear to be a reliable and cost-effective option, whereas denosumab has introduced a simpler dosing regimen and may achieve a linear increase in bone mineral density (BMD) with no plateau being observed, along with continuous anti-fracture efficacy. Abaloparatide, a parathyroid-hormone-related peptide (PTHrP)-analogue, approved by the FDA in April 2017, constitutes the first new anabolic osteoporosis drug in the US for nearly 15 years and has also proven its anti-fracture efficacy. Romosozumab, a sclerostin inhibitor, which induces bone formation and suppresses bone resorption, has also been developed and shown a significant reduction in fracture incidence; however, concerns have arisen with regard to increased cardiovascular risk. 相似文献
The purpose of this work was to investigate the use of an intravascular contrast agent to determine perfusion kinetics in skeletal muscle. A two-compartment kinetic model was used to represent the flux of contrast agent between the intravascular space and extravascular extracellular space (EES). The relationship between the image signal-to-noise ratio (SNR) and errors in estimating permeability surface area product (Ktrans), interstitial volume (ve), and plasma volume (vp) for linear and nonlinear curve-fitting methods was estimated from Monte Carlo simulations. Similar results were obtained for both methods. For an image SNR of 60, the estimated errors in these parameters were 10%, 22%, and 17%, respectively. In vivo experiments were conducted in rabbits to examine physiological differences between these parameters in the soleus (SOL) and tibialis anterior (TA) muscles in the hind limb. Values for Ktrans were significantly higher in the SOL (3.2+/-0.9 vs. 2.0+/-0.5x10(-3) min-1), as were values for vp (3.4+/-0.8 vs. 2.1+/-0.7%). Differences in ve for the two muscles (8.7+/-2.2 vs. 8.5+/-1.6%) were not found to be significant. These results demonstrate that relevant physiological metrics can be calculated in skeletal muscle using MRI with an intravascular contrast agent. 相似文献
The main objectives of the European Committee on Antimicrobial Susceptibility Testing (EUCAST) are to harmonise breakpoints for antimicrobial agents in Europe, and to act as the breakpoint committee for the European Medicines Agency (EMEA) during the registration of new antimicrobial agents. Detailed EUCAST procedures for harmonising and setting breakpoints for antimicrobial agents are available on the EUCAST website. Beginning with the current issue, a series of EUCAST Technical Notes will be published in CMI, based on the rationale documents produced by EUCAST for each of the antimicrobial agents studied, with the aim of highlighting important background information underlying decisions on breakpoints made by EUCAST. 相似文献