Adjuvant bisphosphonates or RANK-ligand inhibitors for patients with breast cancer and bone metastases: A systematic review and network meta-analysis.

Bone-modifying agents like bisphosphonates and receptor activator of nuclear factor kappaß ligand (RANK-L) inhibitors are used as supportive treatments in breast cancer patients with bone metastases to prevent skeletal-related events (SREs). Due to missing head-to-head comparisons, a network meta-analysis was performed to provide a hierarchy of these therapeutic options. Through a systematic literature search, 21 randomized controlled trials (RCTs) that fulfilled the inclusion criteria were identified. To prevent SREs, the ranking through P-scores showed denosumab (RR: 0.62; 95%CI: 0.50-0.76), zoledronic acid (RR: 0.72; 95%CI: 0.61-0.84) and pamidronate (RR: 0.76; 95%CI: 0.67-0.85) to be significantly superior to placebo. Due to insufficient or heterogeneous data, overall survival, quality of life, pain response and adverse events were not able to be analyzed within the network. Although data were sparse on adverse events, the risk of significant adverse events appeared low. The results of this review can therefore be used to formulate clinical studies more precisely in order to standardise and focus on patient-relevant outcomes.

Comparison of extracorporeal shock wave lithotripsy and ureteroscopy in the treatment of ureteral calculi: a prospective study.

146 patients whose ureteral stones did not pass spontaneously participated in a prospective study on optimal management. Patients were offered two treatment options: extracorporeal shock wave lithotripsy (ESWL) and ureteroscopy (URS). The stone was treated with the technique preferred by the patient. In case of treatment failure after first-line therapy, patients again could decide on how to proceed. Stone analysis could be obtained from 72.6% patients. ESWL was the primary treatment in 66.4% patients. In 2 patients, ESWL was the secondary treatment after failed URS. URS was the first-line therapy in 33.6% patients. In 29 patients URS was done after failed ESWL. For analgesia, sedoanalgesia or spinal anesthesia were used. Analgesia was required in 74.2% ESWL and 100% URS sessions. Following ESWL, 70.1% patients became stone free. In 29.9% ESWL failed. Distal stones had a higher failure rate than proximal or mid-ureteral calculi. Distal stones treated without success were significantly larger than those treated successfully. Failures were switched to URS. Stone analysis could be obtained in 26 patients with failed ESWL: 23/26 consisted of pure whewellite or mixed whewellite stones. Clinically relevant complications were not observed. After URS, 94.9% of the patients became stone free. In distal stones, the stone-free rate was 97.5%. There was only 1 relevant complication: a proximal ureteral lesion requiring surgical repair. Our study demonstrates that URS is a safe and highly effective treatment option for ureteral stones. In patients with distal ureteral stones, it should be offered as a first-line treatment. When whewellite is expected as the stone mineral, URS is the treatment of choice.

The effect of amphotericin B on the water and nonelectrolyte permeability of thin lipid membranes.

This paper reports the effects of amphotericin B, a polyene antibiotic, on the water and nonelectrolyte permeability of optically black, thin lipid membranes formed from sheep red blood cell lipids dissolved in decane. The permeability coefficients for the diffusion of water and nonelectrolytes (P(DDi)) were estimated from unidirectional tracer fluxes when net water flow (J(w)) was zero. Alternatively, an osmotic water permeability coefficient (P(f)) was computed from J(w) when the two aqueous phases contained unequal solute concentrations. In the absence of amphotericin B, when the membrane solutions contained equimolar amounts of cholesterol and phospholipid, P(f) was 22.9 +/- 4.6 microsec(-1) and P(DDHDH2O) was 10.8 +/- 2.4 microsec(-1). Furthermore, P(DDi) was < 0.05 microsec(-1) for urea, glycerol, ribose, arabinose, glucose, and sucrose, and sigma(i), the reflection coefficient of each of these solutes was one. When amphotericin B (10(-6)M) was present in the aqueous phases and the membrane solutions contained equimolar amounts of cholesterol and phospholipid, P(DDHDH2O) was 18.1 +/- 2.4 microsec(-1); P(f) was 549 +/- 143 microsec(-1) when glucose, sucrose, and raffinose were the aqueous solutes. Concomitantly, P(DDi) varied inversely, and sigma(i) directly, with the effective hydrodynamic radii of the solutes tested. These polyene-dependent phenomena required the presence of cholesterol in the membrane solutions. These data were analyzed in terms of restricted diffusion and filtration through uniform right circular cylinders, and were compatible with the hypothesis that the interactions of amphotericin B with membrane-bound cholesterol result in the formation of pores whose equivalent radii are in the range 7 to 10.5 A.