The Top 100 Cited Articles in the Microsurgical Treatment for Lymphedema.

BACKGROUND: Evidence-based medicine uses the current best evidence for decisions about patient care. Lymphedema is a chronic debilitating medical condition caused by a dysfunctional lymphatic system. This study analyzes the most cited articles, including the levels of evidence, for the surgical treatment of lymphedema. METHODS: The Web of Science Sci-Expanded Index was utilized to search for surgical treatment of lymphedema. Articles were examined by three independent reviewers and the top 100 articles were determined. The corresponding author, citation count, publication year, topic, study design, level of evidence, journal, country, and institution were analyzed. RESULTS: Since 1970, the top 100 articles have been cited 7,300 times. The average citation count was 68 and standard deviation was 55. The majority was case series (71), followed by retrospective cohort (8), prospective cohort (7), retrospective case-control (5), and randomized controlled trials (2). Based on the "Level of Evidence Pyramid," 71 articles were level IV, 13 articles were level III, and 9 articles were level II. On the Grading of Recommendations Assessment, Development, and Evaluation Scale, there were 71 articles with "very low," 20 articles with "low," and 2 articles with "moderate" quality of evidence. CONCLUSION: The top 100 cited articles were mostly case series and lacked high levels of evidence. Most studies are retrospective case series with short-term outcomes. However, low level evidence for new surgical procedures is to be expected. Current trends suggest the treatment and understanding of lymphedema will continue to improve.

Liposomal packaging generates Wnt protein with in vivo biological activity.

Wnt signals exercise strong cell-biological and regenerative effects of considerable therapeutic value. There are, however, no specific Wnt agonists and no method for in vivo delivery of purified Wnt proteins. Wnts contain lipid adducts that are required for activity and we exploited this lipophilicity by packaging purified Wnt3a protein into lipid vesicles. Rather than being encapsulated, Wnts are tethered to the liposomal surface, where they enhance and sustain Wnt signaling in vitro. Molecules that effectively antagonize soluble Wnt3a protein but are ineffective against the Wnt3a signal presented by a cell in a paracrine or autocrine manner are also unable to block liposomal Wnt3a activity, suggesting that liposomal packaging mimics the biological state of active Wnts. When delivered subcutaneously, Wnt3a liposomes induce hair follicle neogenesis, demonstrating their robust biological activity in a regenerative context.