KCNQ potassium channels modulate Wnt activity in gastro-oesophageal adenocarcinomas.

Voltage-sensitive potassium channels play an important role in controlling membrane potential and ionic homeostasis in the gut and have been implicated in gastrointestinal (GI) cancers. Through large-scale analysis of 897 patients with gastro-oesophageal adenocarcinomas (GOAs) coupled with in vitro models, we find KCNQ family genes are mutated in ∼30% of patients, and play therapeutically targetable roles in GOA cancer growth. KCNQ1 and KCNQ3 mediate the WNT pathway and MYC to increase proliferation through resultant effects on cadherin junctions. This also highlights novel roles of KCNQ3 in non-excitable tissues. We also discover that activity of KCNQ3 sensitises cancer cells to existing potassium channel inhibitors and that inhibition of KCNQ activity reduces proliferation of GOA cancer cells. These findings reveal a novel and exploitable role of potassium channels in the advancement of human cancer, and highlight that supplemental treatments for GOAs may exist through KCNQ inhibitors.

Differentiating Nonpermanent Injectable Fillers: Prevention and Treatment of Filler Complications.

Though the incidence of complications and adverse events with dermatological fillers is inherently low, practitioners should be well versed in both prevention of filler complications and the treatment algorithms for addressing "granulomas," nodules, infection, and vascular compromise. Appropriate preventative measures, coupled with timely and effective treatment, are critically important for patient safety and satisfaction. In addition to the preventive measures and treatment algorithms outlined here, the authors emphasize that the broad classification and treatment of nodules as "granulomas" is likely to lead to ineffective treatment, or worse, unnecessary exposure to incorrect treatment. In practice, nodules are classified and treated based on clinical manifestation (eg, late vs early or noninflammatory vs inflammatory) rather than on histology. Indeed, classification of a nodule as a granuloma requires a histological examination, rarely available (or necessary) in clinical practice to guide treatment. Thus, the apparent inflammatory nature of the nodule and the time of onset should drive treatment approach. The treatment algorithms presented here are based on these clinically meaningful parameters.

Combination Therapy in Midfacial Rejuvenation.

BACKGROUND: Facial aging in the midface reflects cumulative results of multiple intrinsic and extrinsic factors over time. Midfacial rejuvenation procedures can make a positive impact on facial attractiveness and patient satisfaction. OBJECTIVE: To review evidence and clinical experience using combination treatments for midfacial rejuvenation to achieve optimal outcomes. MATERIALS AND METHODS: This article provides a review of published scientific evidence supporting the use of combination therapy in midfacial rejuvenation. In addition, the authors share their cumulative clinical experience and best practices for combination treatments in the midface. RESULTS: Clinical experience and evidence shows that combining multiple aesthetic therapies targeting multiple aspects of the aging process provides optimal results, with greater overall efficacy and a higher level of patient satisfaction.

Poly-L-lactic acid injection for HIV-associated facial lipoatrophy: treatment principles, case studies, and literature review.

BACKGROUND: Most HIV-positive patients receiving highly active antiretroviral therapy develop facial lipoatrophy soon after commencing treatment. Attempts to correct lipoatrophy through autologous fat transfer or the use of temporary, semipermanent, or permanent fillers have achieved some benefits, but either do not have lasting effects, do not treat some areas effectively, or have other disadvantages. OBJECTIVE: The purpose of this article is to outline the treatment principles for use of poly-L-lactic acid (PLLA) in HIV-associated facial lipoatrophy since its emergence in 1999 and review the relevant literature, with particular emphasis on investigations of the incidence of subcutaneous papule formation after PLLA treatment. METHODS: The principles of treating facial lipoatrophy with PLLA, including product preparation, patient preparation, and injection technique, are reviewed. Two case studies and results are presented as typical examples of treatment and results. A literature discussion focuses on changes in the incidence of papule formation after PLLA treatment. RESULTS: In the representative cases presented, 2 white men in their forties with facial lipoatrophy who had been HIV-positive for more than 10 years received 2 vials of PLLA in each of 5 treatments spaced 4 weeks apart. Results are shown 4 weeks after the final treatment. No papules were reported in the 12-month follow-up period. CONCLUSIONS: Early investigations of PLLA for the treatment of HIV-associated facial lipoatrophy reported a significantly high incidence of subcutaneous papule formation. As experience with PLLA has increased, the incidence of papule formation has dropped dramatically. The proper dilution, adequate hydration time, proper placement of the product, sufficient intervals between treatments, and posttreatment massage all have contributed to this decrease.