Serum alpha-fetoprotein and clinical outcomes in patients with advanced hepatocellular carcinoma treated with ramucirumab

Background Post hoc analyses assessed the prognostic and predictive value of baseline alpha-fetoprotein (AFP), as well as clinical outcomes by AFP response or progression, during treatment in two placebo-controlled trials (REACH, REACH-2).Methods Serum AFP was measured at baseline and every three cycles. The prognostic and predictive value of baseline AFP was assessed by Cox regression models and Subpopulation Treatment Effect Pattern Plot method. Associations between AFP (≥ 20% increase) and radiographic progression and efficacy were assessed.Results Baseline AFP was confirmed as a continuous (REACH, REACH-2; p < 0.0001) and dichotomous (≥400 vs. <400 ng/ml; REACH, p < 0.01) prognostic factor, and was predictive for ramucirumab survival benefit in REACH (p = 0.0042 continuous; p < 0.0001 dichotomous). Time to AFP (hazard ratio [HR] 0.513; p < 0.0001) and radiographic (HR 0.549; p < 0.0001) progression favoured ramucirumab. Association between AFP and radiographic progression was shown for up to 6 (odds ratio [OR] 5.1; p < 0.0001) and 6–12 weeks (OR 1.8; p = 0.0065). AFP response was higher with ramucirumab vs. placebo (p < 0.0001). Survival was longer in patients with an AFP response than patients without (13.6 vs. 5.6 months, HR 0.451; 95% confidence interval, 0.354–0.574; p < 0.0001).Conclusions AFP is an important prognostic factor and a predictive biomarker for ramucirumab survival benefit. AFP ≥ 400 ng/ml is an appropriate selection criterion for ramucirumab.Clinical Trial Registration ClinicalTrials.gov, REACH ({"type":"clinical-trial","attrs":{"text":"NCT01140347","term_id":"NCT01140347"}}NCT01140347) and REACH-2 ({"type":"clinical-trial","attrs":{"text":"NCT02435433","term_id":"NCT02435433"}}NCT02435433).Subject terms: Oncology, Biomarkers     

Do men with normal testosterone–oestradiol ratios benefit from letrozole for the treatment of male infertility?

Research question

Previous studies of aromatase inhibitors on male infertility have focused on men with low testosterone–oestradiol ratio of less than 10. Can aromatase inhibitors improve spermatogenesis in men with idiopathic male infertility with normal testosterone–oestradiol ratio?

Fatigue resistance of yttria‐stabilized tetragonal zirconia polycrystal clasps for removable partial dentures

With the rapid development of computer‐aided design/computer‐aided manufacturing (CAD /CAM ) systems, the application of zirconia in removable partial dentures is expected to expand. Clasps composed of zirconia should improve esthetics without inducing the risk of metal allergy. The aim of this study was to examine the fatigue resistance of yttria‐stabilized tetragonal zirconia polycrystal (Y‐TZP) clasps for removable partial dentures. Yttria‐stabilized tetragonal zirconia polycrystal and cobalt‐chromium (Co‐Cr) alloy were prepared using CAD /CAM systems. Specimens were either of the semicircular type or of the flat type, with cross‐sectional areas of taper ratios of 0.50, 0.75, and 1.00. All specimens were tested using the cantilever test and the constant displacement fatigue test, and data were analyzed using ANOVA . During the cantilever test, the maximum displacement prior to fracture was greater than the required undercut, and the semicircular‐type specimen exhibited a higher fracture load than the flat type. None of the specimens displayed permanent deformation and showed almost the same degree of deformation after fatigue testing. A lower taper ratio was associated with lower average load values and greater displacement. Within the limitations of this study, it was possible to conclude that Y‐TZP provides the required undercut and adequate retentive force for removable partial denture clasps. Additionally, Y‐TZP and Co‐Cr alloy had almost the same degree of deformation even after the simulated lifespan of removable partial dentures.