Faculty Bibliography

PURPOSE/OBJECTIVE:Free tissue transfer after lower extremity trauma is associated with notoriously high complication rates. Theoretically, the inclusion of a cutaneous paddle on muscle free flaps may improve clinical flap monitoring. The effect of skin paddle presence on muscle free flap salvage outcomes after take-back was examined. METHODS:Retrospective query of our institutional free-flap registry (1979-2016) identified 362 muscle-based flaps performed for soft tissue coverage after below-knee trauma. Primary outcome measures were perioperative complications, specifically take-back indications, timing, and flap salvage rates. Univariate and multivariate regression analyses were performed where appropriate. RESULTS:The most common flaps were latissimus dorsi (166; 45.9%), rectus abdominis (123; 34%), and gracilis (42; 11.6%) with 90 flaps (24.9%) including skin paddles. Take-backs for vascular compromise occurred in 44 flaps (12.2%), of which 39% contained a skin paddle while 61% did not. Overall salvage rate was 20.5%, with 31.8% partial failures and 47.7% total flap losses. Muscle flaps with skin paddles were more likely to return to the operating room within 48 hours postoperatively than those without (57.1% vs 18.2%, P = 0.036). After take-back, significantly more muscle flaps with skin paddles were salvaged compared with muscle flaps without paddles (35.7% vs 4.5%, P = 0.024). Similarly, more muscle-only flaps after take-back failed compared with their counterparts with skin paddles (95.5% vs 65.3%, P = 0.024). CONCLUSIONS:Muscle flaps with a cutaneous paddle were associated with earlier return to the operating room and more successful flap salvage after take-back compared with muscle-only flaps. These findings suggest that skin paddle presence may improve clinical flap monitoring and promote recognition and treatment of microvascular compromise in lower extremity reconstruction.

The current U.S. demographic shift toward an older population and the importance of intervening before conditions become severe warrant a concerted effort to ease the burden of access to healthcare for older adults. With regard to oral healthcare, more integrated services for older adults are needed to effectively serve their complex medical and dental needs. Using an agent-based simulation model, this paper examines the influence of social ties and transportation mode choices on opportunities for older adults to participate in community-based preventive screening events and access needed oral healthcare. This approach accounts for the heterogeneity of behavior that arises for a population exhibiting diversity in terms of social factors, including socioeconomic means and social support. In the context of older adults living in urban environments, the availability of different transportation modes ought to be taken into consideration. To explore alternative scenarios for the accessibility of preventive screening events offered at senior centers in northern Manhattan, an agent-based model (ABM) was created with a geographic information system (GIS) to simulate the influence of social ties and transportation choices on older adults seeking preventive screening services and oral healthcare. Results of simulation experiments indicate preferences for public transportation and inequities in accessibility that may be mitigated with social support. This simulation model offers a way to explore social support as an important factor in making transportation mode choices that mediate oral healthcare accessibility and thus oral health outcomes for older adults.

Ionizing radiation is a known carcinogen. Its damaging effects can be deterministic or stochastic. Deterministic effects occur only after radiation exposure thresholds are reached, but stochastic effects are random, and there is no known threshold below which harmful effects will not occur. Therefore, the use of ionizing radiation in orthodontic treatment should bring a benefit to the patient that outweighs the risks. No legally binding statutes, rules, or regulations provide explicit radiographic prescription protocols for orthodontic practice. The objective of this article was to discuss guidelines and risk management strategies for appropriate and defensible use of ionizing radiation in orthodontics. Guidelines are discussed for radiographic acquisition at different points along the orthodontic treatment timeline. In addition, risk management strategies and best practices are presented regarding adequate and defensible radiographic interpretation. These guidelines are not rigid and do not establish standards of care; they should be modified as necessary for each patient and each clinical encounter.

This article focuses on flap-related complications after creation of a neophallus for transgender individuals. It outlines the most frequently used flaps for this procedure and how flap-related complications can affect the overall outcome of the phalloplasty. With surgeons staging the procedure in different stages, it is important to understand the different strategies and the implication a flap-related complication can have on the end result and how it may be prevented.

Angiogenesis is a critical aspect of wound healing. We investigated the role of keratinocytes in promoting angiogenesis in mice with lineage specific deletion of the transcription factor FOXO1. The results indicate that keratinocyte-specific deletion of Foxo1 reduces VEGFA expression in mucosal and skin wounds and leads to the reduced endothelial cell proliferation, reduced angiogenesis and impaired re-epithelialization and granulation tissue formation. In vitro FOXO1 was needed for VEGFA transcription and expression. In a porcine dermal wound healing model that closely resembles healing in humans, local application of a FOXO1 inhibitor reduced angiogenesis. This is the first report that FOXO1 directly regulates VEGFA expression and that FOXO1 is needed for normal angiogenesis during wound healing.

Abnormal pigmentation is commonly seen in the wound scar. Despite advancements in the research of wound healing, little is known about the repopulation of melanocytes in the healed skin. Previous studies have demonstrated the capacity of melanocyte stem cells (McSCs) in the hair follicle to contribute skin epidermal melanocytes following injury in mice and humans. Here, we focused on the Wnt pathway, known to be a vital regulator of McSCs in efforts to better understand the regulation of follicle-derived epidermal melanocytes during wound healing. We showed that transgenic expression of Wnt inhibitor, Dkk1 in melanocytes reduced epidermal melanocytes in the wound scar. Conversely, forced activation of Wnt signaling by genetically stabilizing β-catenin in melanocytes increases epidermal melanocytes. Furthermore, we reveal that deletion of Wntless, a gene required for Wnt ligand secretion, within epithelial cells, results in failure in activating Wnt signaling in adjacent epidermal melanocytes. These results reveal the essential function of extrinsic Wnt ligands to initiate Wnt signaling in follicle-derived epidermal melanocytes during wound healing. Collectively, our results suggest the potential for Wnt signal regulation to promote melanocyte regeneration and provide a potential molecular window to promote proper melanocyte regeneration following wounding as well as in conditions such as vitiligo.

Current pharmacologic regimens in transplantation prevent allograft rejection through systemic recipient immunosuppression but are associated with severe morbidity and mortality. The ultimate goal of transplantation is the prevention of allograft rejection while maintaining recipient immunocompetence. We hypothesized that allografts could be engineered ex vivo (after allotransplant procurement but before transplantation) by using mesenchymal stem cell-based therapy to generate localized immunomodulation without affecting systemic recipient immunocompetence. To this end, we evaluated the therapeutic efficacy of bone marrow-derived mesenchymal stem cells in vitro and activated them toward an immunomodulatory fate by priming in inflammatory or hypoxic microenvironments. Using an established rat hindlimb model for allotransplantation, we were able to significantly prolong rejection-free allograft survival with a single perioperative ex vivo infusion of bone marrow-derived mesenchymal stem cells through the allograft vasculature, in the absence of long-term pharmacologic immunosuppression. Critically, transplanted rats rejected a second, nonengineered skin graft from the same donor species to the contralateral limb at a later date, demonstrating that recipient systemic immunocompetence remained intact. This study represents a novel approach in transplant immunology and highlights the significant therapeutic opportunity of the ex vivo period in transplant engineering.

BACKGROUND:While the US population overall has experienced improvements in oral health over the past 60 years, oral diseases remain among the most common chronic conditions across the life course. Further, lack of access to oral health care contributes to profound and enduring oral health inequities worldwide. Vulnerable and underserved populations who commonly lack access to oral health care include racial/ethnic minority older adults living in urban environments. The aim of this study was to use a systematic approach to explicate cause and effect relationships in creating a causal map, a type of concept map in which the links between nodes represent causality or influence. METHODS:To improve our mental models of the real world and devise strategies to promote oral health equity, methods including system dynamics, agent-based modeling, geographic information science, and social network simulation have been leveraged by the research team. The practice of systems science modeling is situated amidst an ongoing modeling process of observing the real world, formulating mental models of how it works, setting decision rules to guide behavior, and from these heuristics, making decisions that in turn affect the state of the real world. Qualitative data were obtained from focus groups conducted with community-dwelling older adults who self-identify as African American, Dominican, or Puerto Rican to elicit their lived experiences in accessing oral health care in their northern Manhattan neighborhoods. RESULTS:The findings of this study support the multi-dimensional and multi-level perspective of access to oral health care and affirm a theorized discrepancy in fit between available dental providers and patients. The lack of information about oral health at the community level may be compromising the use and quality of oral health care among racial/ethnic minority older adults. CONCLUSIONS:Well-informed community members may fill critical roles in oral health promotion, as they are viewed as highly credible sources of information and recommendations for dental providers. The next phase of this research will involve incorporating the knowledge gained from this study into simulation models that will be used to explore alternative paths toward improving oral health and health care for racial/ethnic minority older adults.