BackgroundBisphosphonates have exhibited anti-tumor activity in non-small cell lung cancer (NSCLC). We aimed to evaluate whether the combination of bisphosphonates with tyrosine kinase inhibitors of EGFR (EGFR-TKIs) could obtain a synergistic effect on advanced NSCLC patients with EGFR mutations.MethodsBetween January 2008 and October 2013, 114 advanced EGFR mutations NSCLC patients who received EGFR-TKIs as first-line therapy were recruited from two cancer centers. Patients were separated into EGFR-TKIs alone or EGFR-TKIs plus bisphosphonates (combination) group. Median progression free survival (mPFS), median overall survival (mOS) distributions and survival curves were analyzed.ResultsAmong the 114 patients, 62 had bone metastases (19 patients treated with EGFR-TKIs, 43 patients treated with EGFR-TKIs + bisphosphonates). Median PFS and OS were significantly improved in combination group compared with EGFR-TKIs group (mPFS: 15.0 vs 7.3 months, P = 0.0017; mOS: 25.2 vs 10.4 months, P = 0.0015) in patients with bone metastases. Among the 71 patients (19 patients with bone metastases) treated with EGFR-TKIs alone, patients with bone metastases had poor survival prognosis (mPFS:7.3 vs 12.1 months, P = 0.0434; mOS:10.4 vs 22.0 months, P = 0.0036). The survival of patients with bone metastases who received EGFR-TKIs plus bisphosphonates therapy was non-inferior to patients without bone metastases treated with EGFR-TKIs alone (mPFS: 15.0 vs 12.1 months, p = 0.1871; mOS: 25.2 vs 22.0 months, p = 0.9798).ConclusionsConcomitant use of bisphosphonates and EGFR-TKIs improves therapeutic efficacy and brings survival benefits to NSCLC patients with EGFR mutation and bone metastases.

This in vitro study aimed to use failure stress and implant abutment interface (IAI) microgap size to find the compromised axial angle range of angulated zirconia abutments with a titanium base in narrow diameter implants in the esthetic region. A three-dimensional (3D) finite element model of maxillary central incisor implant prosthesis was reconstructed. Angulated zirconia abutments (0 , 15 , 30 , and À 15 ) with a titanium base in narrow diameter implants (3.3 Â 12 mm, Bone level, Roxolid SLActive, Straumann AG, Switzerland) were designed to simulate clinical scenarios of buccal inclination 0 , 15 , and 30 , and palatal inclination 15 of the implant long axis. Straight titanium abutment and pure titanium implant were used as two control groups. An oblique force at 30 inclination to the long axis of the crown was applied 3 mm below the incisal edge on the palatal surface of the prosthesis.Under simulated dynamic chewing force, the stress distribution of the implant components and surrounding bone were investigated. The relative micromotion displacement between the implant and abutment models at the IAI area was recorded, and the influence of tightening torque on the IAI microgap was evaluated. The angulation of the zirconia abutment could affect the stress value and IAI microgap of implant restorations. When the zirconia abutment angle increased from À15 to 30 , the stress on the central screw, titanium base, and surrounding bone tissue gradually increased by 9%, 20%, and 23%, respectively. The stress levels of the 30 zirconia abutment group showed the risk of exceeding the threshold. When the long axis of the implant was inclined in the palatal direction, the À15 angle abutment reduced the stress by 3% and reduced the strain level of the implant system by 17% and the surrounding bone tissue by 26%. Under simulated dynamic chewing load, the displacement between the implants and the abutment occurred in each group of the implant system, and the amplitude of the micromotion fluctuated with the change in Yuqiang Zhang and Ping Yu contributed equally to this article and should be regarded as co-first authors.

Glass-fibre-reinforced polyetherketoneketone (PEKK-GF) shows great potential for application as a dental implant restoration material; however, its surface bioinertness and poor antibacterial properties limit its integration with peri-implant soft tissue, which is critical in the long-term success of implant restoration. Herein, functional magnesium (Mg) and silver (Ag) ions were introduced into PEKK-GF by plasma immersion ion implantation (PIII). Surface characterisation confirmed that the surface morphology of PEKK-GF was not visibly affected by PIII treatment. Further tests revealed that PIII changed the wettability and electrochemical environment of the PEKK-GF surface and enabled the release of Mg2+ and Ag+ modulated by Giavanni effect. In vitro experiments showed that Mg/Ag PIII-treated PEKK-GF promoted the proliferation and adhesion of human gingival fibroblasts and upregulated the expression of adhesion-related genes and proteins. In addition, the treated samples inhibited the metabolic viability and adhesion of Streptococcus mutans and Porphyromonas gingivalis on their surfaces, distorting bacterial morphology. Mg/Ag PIII surface treatment improved the soft tissue integration and antibacterial activities of PEKK-GF, which will further support and broaden its adoption in dentistry.

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