Patents for the Plastic Surgeon: A Primer.

ABSTRACT: Although innovation and entrepreneurship are complementary in the process of creating new products, plastic surgeons are frequently discouraged by the challenges associated with the regulatory and administrative environments in patent filing. The following primer provides a step-by-step guide for understanding patents and outlines the steps and costs involved in patent filing. To improve opportunities for successful patent filing, we elaborate on some of the common pitfalls in the process, including the timing of public disclosure, conducting a private art search, selecting a patent attorney or agent, determining the level of inventor involvement, and navigating academic and employment contracts. The innovative drive in plastic surgery provides a strong impetus for strengthening knowledge about patents and patent filing in order to support efforts for providing high-value patient care.

The Evolving Landscape of Gene Therapy in Plastic Surgery.

With the rapid rise of personalized genomic sequencing and clustered regularly interspaced short palindromic repeat (CRISPR) technology, previous gaps in gene therapy are beginning to be bridged, paving the way for increasing clinical applicability. This article aims to provide an overview of the fundamentals of gene therapy and discuss future potential interventions relevant to plastic surgeons. These interventions include enhancing tissue regeneration and healing, as well as modifying disease processes in congenital anomalies. Though clinical applications are still on the horizon, a deeper understanding of these new advances will help plastic surgeons understand the current landscape of gene therapy and stay abreast of future opportunities.

MicroRNA Microarray Profiling in Infantile Hemangiomas.

Objective: MicroRNAs are short, noncoding RNA molecules that negatively regulate the stability and translational efficiency of target mRNAs. They are critical regulators of growth and development. Our aim was to identify microRNAs involved in the growth and regulation of infantile hemangiomas. In addition, we searched for the presence of Piwi-interacting RNAs in hemangioma tissue as another regulator of infantile hemangiomas. Methods: RNA was extracted from hemangioma specimens from 3 clinical, age-based categories: proliferative (N = 16), quiescent (N = 8), and involuting (N = 9). RNAs from human dermal microvascular endothelial cells were used as controls. MicroRNA microarray was performed, and the expression profiles of the hemangiomas and endothelial cells were compared using the t test. 5' End-labeling of RNA of our hemangioma specimens was performed for Piwi-interacting RNA detection. Results: Analysis confirmed statistically significant downregulated (N = 18) and upregulated (N = 15) microRNAs. Piwi-interacting RNA analysis did not detect Piwi-interacting RNA transcripts in the hemangioma specimens. Conclusions: The differential expression of microRNAs found in our hemangioma specimens provides insight into the regulation of hemangioma formation and proliferation, quiescence, and fibrofatty involution. Piwi-interacting RNA transcripts were not detected in the hemangioma specimens. These novel findings will help in establishing new therapeutic and diagnostic initiatives for these tumors.

Cadaveric Study of a Z-Plasty Modification to the Moberg Flap for Increased Advancement and Decreased Morbidity.

BACKGROUND: The Moberg advancement flap is a well-established tool to provide sensate, vascularized tissue for thumb reconstruction. Modifications providing additional length have been described, but no studies have examined how much additional advancement can be achieved consistently, and at what cost. The authors hypothesized that Z-plasty modification at the base of the Moberg flap would allow additional advancement compared with the traditional technique, and maintain primary closure of the donor-site and avoid additional morbidity. METHODS: Standard Moberg flaps were performed and advancement was measured on 20 cadaver specimens. Ten flaps were then modified with the O'Brien technique of incising proximally and skeletonizing the neurovascular bundles. The other 10 flaps were modified with Z-plasties at the base of the thumb. Differences in distance of advancement were compared, as was the ability to primarily close donor sites. RESULTS: Average advancement for Moberg flaps was 7.3 ± 1.2 mm, compared with 15.0 ± 2.5 mm for the O'Brien modification (p < 0.01) and 11.3 ± 1.7 mm for the Z-plasty modification (p < 0.01). CONCLUSIONS: Although the O'Brien modification allows approximately 50 percent further advancement than the Z-plasty modification compared with the standard Moberg flaps, the increase correlates to a large area of exposed neurovascular bundles at the volar base of the thumb, which requires secondary coverage. However, all Z-plasty donor-sites could be closed primarily. Primary closure of all donor sites will decrease healing time, wound complications, digital nerve sensitivity, and cosmetic appearance. This study is the first to show a significant increase in Moberg flap advancement using Z-plasty lengthening at the thumb base while avoiding any increased morbidity.

A Common Polymorphism within the IGF2 Imprinting Control Region Is Associated with Parent of Origin Specific Effects in Infantile Hemangiomas.

Infantile hemangioma (IH) is the most common tumor of the pediatric age group, affecting up to 4% of newborns ranging from inconsequential blemishes, to highly aggressive tumors. Following well defined growth phases (proliferative, plateau involutional) IH usually regress into a fibro-fatty residuum. Despite the high prevalence of IH, little is known regarding the pathogenesis of disease. A reported six fold decrease in IGF2 expression (correlating with transformation of proliferative to involuted lesions) prompted us to study the IGF-2 axis further. We demonstrate that IGF2 expression in IH is strongly related to the expression of a cancer testes and suspected oncogene BORIS (paralog of CTCF), placing IH in the unique category of being the first known benign BORIS positive tumor. IGF2 expression was strongly and positively related to BORIS transcript expression. Furthermore, a stronger association was made when comparing BORIS levels against the expression of CTCF via either a percentage or difference between the two. A common C/T polymorphism at CTCF BS6 appeared to modify the correlation between CTCF/BORIS and IGF2 expression in a parent of origin specific manner. Moreover, these effects may have phenotypic consequences as tumor growth also correlates with the genotype at CTCF BS6. This may provide a framework for explaining the clinical variability seen in IH and suggests new insights regarding CTCF and BORIS related functionality in both normal and malignant states.

Infantile hemangiomas exhibit neural crest and pericyte markers.

Infantile hemangiomas (IHs) are the most common benign tumors of infancy and occur with greater than 60% prevalence on the head and neck. Despite their prevalence, little is known about the pathogenesis of this disease. Given the predilection of hemangioma incidence on the face and its nonrandom distribution on embryological fusion plates, we postulated that IHs are derived from pericytes of the neural crest. We performed an analysis on 15 specimens at various stages of the IH progression. Experiments performed included immunohistochemical staining, immunofluorescent staining, quantitative real-time polymerase chain reaction, and flow cytometry. We analyzed a number of cell markers using these methods, including cell markers for the neural crest, pericytes, endothelial cells, stem cells, and the placenta. We observed that neural crest markers such as NG2 and nestin were expressed in the hemangioma samples, in addition tomultiple pericytes markers including δ-like kinase, smooth muscle actin, calponin, and CD90. Stem cell markers such as c-myc, oct4, nanog, and sox2 were also more highly expressed in hemangioma samples compared to controls. Our work demonstrates that hemangiomas express pericyte, neural crest, and stem cell markers suggesting a possible pathogenetic mechanism.