Purpose This phase III study evaluated ribociclib plus fulvestrant in patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer who were treatment naïve or had received up to one line of prior endocrine therapy in the advanced setting. Patients and Methods Patients were randomly assigned at a two-to-one ratio to ribociclib plus fulvestrant or placebo plus fulvestrant. The primary end point was locally assessed progression-free survival. Secondary end points included overall survival, overall response rate, and safety. Results A total of 484 postmenopausal women were randomly assigned to ribociclib plus fulvestrant, and 242 were assigned to placebo plus fulvestrant. Median progression-free survival was significantly improved with ribociclib plus fulvestrant versus placebo plus fulvestrant: 20.5 months (95% CI, 18.5 to 23.5 months) versus 12.8 months (95% CI, 10.9 to 16.3 months), respectively (hazard ratio, 0.593; 95% CI, 0.480 to 0.732; P< .001). Consistent treatment effects were observed in patients who were treatment naïve in the advanced setting (hazard ratio, 0.577; 95% CI, 0.415 to 0.802), as well as in patients who had received up to one line of prior endocrine therapy for advanced disease (hazard ratio, 0.565; 95% CI, 0.428 to 0.744). Among patients with measurable disease, the overall response rate was 40.9% for the ribociclib plus fulvestrant arm and 28.7% for placebo plus fulvestrant. Grade 3 adverse events reported in ≥ 10% of patients in either arm (ribociclib plus fulvestrant v placebo plus fulvestrant) were neutropenia (46.6% v 0%) and leukopenia (13.5% v 0%); the only grade 4 event reported in ≥ 5% of patients was neutropenia (6.8% v 0%). Conclusion Ribociclib plus fulvestrant might represent a new first- or second-line treatment option in hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer.

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Conductive polymers are promising for bone regeneration because they can regulate cell behavior through electrical stimulation; moreover, they are antioxidative agents that can be used to protect cells and tissues from damage originating from reactive oxygen species (ROS). However, conductive polymers lack affinity to cells and osteoinductivity, which limits their application in tissue engineering. Herein, an electroactive, cell affinitive, persistent ROS‐scavenging, and osteoinductive porous Ti scaffold is prepared by the on‐surface in situ assembly of a polypyrrole‐polydopamine‐hydroxyapatite (PPy‐PDA‐HA) film through a layer‐by‐layer pulse electrodeposition (LBL‐PED) method. During LBL‐PED, the PPy‐PDA nanoparticles (NPs) and HA NPs are in situ synthesized and uniformly coated on a porous scaffold from inside to outside. PDA is entangled with and doped into PPy to enhance the ROS scavenging rate of the scaffold and realize repeatable, efficient ROS scavenging over a long period of time. HA and electrical stimulation synergistically promote osteogenic cell differentiation on PPy‐PDA‐HA films. Ultimately, the PPy‐PDA‐HA porous scaffold provides excellent bone regeneration through the synergistic effects of electroactivity, cell affinity, and antioxidative activity of the PPy‐PDA NPs and the osteoinductivity of HA NPs. This study provides a new strategy for functionalizing porous scaffolds that show great promise as implants for tissue regeneration.

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Hydroxyapatite (HA) coatings on titanium (Ti) substrates have attracted much attention owing to the combination of good mechanical properties of Ti and superior biocompatibility of HA. Incorporating silver (Ag) into HA coatings is an effective method to impart the coatings with antibacterial properties. However, the uniform distribution of Ag is still a challenge and Ag particles in the coatings are easy to agglomerate, which in turn affects the applications of the coatings. In this study, we employed pulsed electrochemical deposition to co-deposit HA and Ag simultaneously, which realized the uniform distribution of Ag particles in the coatings. This method was based on the use of a well-designed electrolyte containing Ag ions, calcium ions and L-cysteine, in which cysteine acted as the coordination agent to stabilize Ag ions. The antibacterial and cell culture tests were used to evaluate the antibacterial properties and biocompatibility of HA/Ag composite coatings, respectively. The results indicated the as-prepared coatings had good antibacterial properties and biocompatibility. However, an appropriate silver content should be chosen to balance the biocompatibility and antibacterial properties. Heat treatments promoted the adhesive strength and enhanced the biocompatibility without sacrificing the antibacterial properties of the HA/Ag coatings. In summary, this study provided an alternative method to prepare bioactive surfaces with bactericidal ability for biomedical devices.

Proximal crescentic metatarsal osteotomy is a clinically successful technique for correcting metatarsus primus varus in hallux valgus surgery. However, there have been instances of dorsal elevation of the metatarsal head with this technique. Mechanical testing on 10 matched pairs of cadaver feet was performed to evaluate a new technique combining a biplanar closing wedge osteotomy and plantar plate fixation versus crescentic metatarsal osteotomy. The specimens were tested in cantilever-bending mode on an MTS Mini Bionix test frame. The mean load-to-failure values were 127.2 +/- 81.9 N (SD) for biplanar osteotomy with plate fixation and 44.9 +/- 43.3 N for crescentic osteotomy (P = 0.019); the mean stiffness values at the initial portion of the load-deflection curve were 83.11 +/- 73.76 N/mm and 31.95 +/- 43.00 N/mm, respectively (P = 0.012). The biplanar wedge osteotomy with plantar plate fixation demonstrated significantly stronger fixation than the crescentic osteotomy, with higher mean load-to-failure and stiffness values. This newly described technique may provide an acceptable alternative for patients at risk for dorsal elevation of the metatarsal, particularly those who are noncompliant or have osteopenia. Clinical study will determine whether this new technique offers satisfactory long-term results.

In the present study, surface functional groups of titanium surfaces gone through different treatments, including acid etched treatment (AE), nitric acid treatment (NT), heat treatment (HT), and alkali treatment (AT), and their behaviors in vitro and in vivo was thoroughly studied by spectroscopic analysis. In vitro and in vivo results revealed that the rank of bioactivity of various surfaces was AE < NT < HT < AT. XPS analysis indicated that AT greatly increased the OH group concentration on the titanium surface whereas HT reduced the OH group concentration. Thus, OH group difference could not be a good explanation of bioactivity difference. On the other hand, ToF-SIMS analysis demonstrated the TiOH þ /Ti þ ratios of various surfaces correlated well with the bioactivity and the surface energies, which implied that Ti-OH could play an important role in the bioactivity. This detail investigation of the relationship between surface functional groups and surface bioactivity could help us to broaden the knowledge about the mechanism of bioactivity and to design next generation bioactive materials.2007 Wiley Periodicals, Inc. J Biomed Mater Res 84A: [523][524][525][526][527][528][529][530][531][532][533][534] 2008

In this study, synergy between graphene platelets (GnPs) and carbon nanotubes (CNTs) in improving lap shear strength and electrical conductivity of epoxy composite adhesives is demonstrated. Adding two-dimensional GnPs with one-dimensional CNTs into epoxy matrix helped to form global three-dimensional network of both GnPs and CNTs, which provide large contact surface area between the fillers and the matrix. This has been evidenced by comparing the mechanical properties and electrical conductivity of epoxy/GnP, epoxy/CNT, and epoxy/GnP-CNT composites. Scanning electron microscopic images of lap shear fracture surfaces of the composite adhesives showed that GnP-CNT hybrid nanofillers demonstrated better interaction to the epoxy matrix than individual GnP and CNT. The lap shear strength of epoxy/GnP-CNT composite adhesive was 89% higher than that of the neat epoxy adhesive, compared with only 44 and 30% increase in the case of epoxy/GnP and epoxy/CNT composite adhesives, respectively. Electrical percolation threshold of epoxy/GnP-CNT composite adhesive is recorded at 0.41 vol %, which is lower than epoxy/GnP composite adhesive (0.58 vol %) and epoxy/CNT composite adhesive (0.53 vol %), respectively.