Lipofilling of the upper eyelid to treat paralytic lagophthalmos.

Lagophthalmos is one of the most unpleasant and dangerous conditions that affect patients with facial palsy. The lack of ocular protection leads to corneal problems (such as conjunctival infections, acute and chronic keratitis, corneal ulcerations, and blindness). A dynamic reanimation of blinking eyelids is the therapeutic gold standard. However, success is not guaranteed with these dynamic techniques; even if results are good, blinking is usually restored within a year of the initial operation. Procedures that act more rapidly and have a higher success rate are needed. We proposed that lipofilling of the upper eyelid would improve eye closure, exploit the advantages of using autologous fat, and avoid the risks of exposure or migration associated with loading the lid with gold. Between 2012 and September 2018, we did upper eyelid lipofilling procedures for 75 patients with unilateral facial palsy. The main favourable result of lipofilling of the upper lid was the immediate improvement in corneal discomfort. Everybody described a partial to total increase in corneal comfort postoperatively. In the treatment of paralytic lagophthalmos, lipofilling of the upper eyelid produces favourable aesthetic and functional results, ocular health is restored, and the patients' quality of life is improved.

Panobinostat synergizes with zoledronic acid in prostate cancer and multiple myeloma models by increasing ROS and modulating mevalonate and p38-MAPK pathways.

Patients with advanced prostate cancer (PCa) and multiple myeloma (MM) have limited long-term responses to available therapies. The histone deacetylase inhibitor panobinostat has shown significant preclinical and clinical anticancer activity in both hematological and solid malignancies and is currently in phase III trials for relapsed MM. Bisphosphonates (BPs), such as zoledronic acid (ZOL), inhibit osteoclast-mediated bone resorption and are indicated for the treatment of bone metastasis. BPs, including ZOL, have also shown anticancer activity in several preclinical and clinical studies. In the present report, we found a potent synergistic antiproliferative effect of panobinostat/ZOL treatment in three PCa and three MM cell lines as well as in a PCa ZOL-resistant subline, independently of p53/KRAS status, androgen dependency, or the schedule of administration. The synergistic effect was also observed in an anchorage-independent agar assay in both ZOL-sensitive and ZOL-resistant cells and was confirmed in vivo in a PCa xenograft model. The co-administration of the antioxidant N-acetyl-L-cysteine blocked the increased reactive oxygen species generation and apoptosis observed in the combination setting compared with control or single-agent treatments, suggesting that oxidative injury plays a functional role in the synergism. Proapoptotic synergy was also partially antagonized by the addition of geranyl-geraniol, which bypasses the inhibition of farnesylpyrophosphate synthase by ZOL in the mevalonate pathway, supporting the involvement of this pathway in the synergy. Finally, at the molecular level, the inhibition of basal and ZOL-induced activation of p38-MAPK by panobinostat in sensitive and ZOL-resistant cells and in tumor xenografts could explain, at least in part, the observed synergism.