Faculty Bibliography
Searched for:
in-biosketch:true
person:ceradd01
Total Results:
121
The Public Face of Transplantation: The Potential of Education to Expand the Face Donor Pool
BACKGROUND:Despite the growing success of facial transplantation, organ donor shortages remain challenging. Educational health campaigns can effectively inform the general public and institute behavioral modifications. A brief educational introduction to facial transplantation may positively influence the public's position on facial donation. METHODS:The authors anonymously surveyed 300 participants, gathering basic demographic information, donor registration status, awareness of facial transplantation, and willingness to donate solid organs and facial allografts. Two-hundred of these participants were presented an educational video and subsequently resurveyed on facial donation. Factorial parametric analyses were performed to compare exposure responses before and after watching video exposure. RESULTS:Among participants completing the survey alone (control group), 49 percent were registered donors, 78 percent reported willingness to donate solid organs, and 52 percent reported willingness to donate facial allograft. Of participants who watched the video (video group) 52 percent were registered; 69 and 51 percent were willing to donate solid organs and face, respectively. Following educational intervention, 69 percent of participants in the video group reported willingness to donate facial tissue, an 18 percent increase (p < 0.05), that equated to those willing to donate solid organs. The greatest increase was observed among younger participants (23 percent); women (22 percent); Jewish (22 percent), Catholic (22 percent), and black/African American (25 percent) participants; and respondents holding a higher degree. No significant differences according to gender or ethnicity were observed. CONCLUSION/CONCLUSIONS:Educational interventions hold much promise for increasing the general public's awareness of facial transplantation and willingness to participate in donation of facial allografts.
PMID: 29280879
ISSN: 1529-4242
CID: 2895412
Microenvironmental cues enhance mesenchymal stem cell-mediated immunomodulation and regulatory T-cell expansion
Mesenchymal stem cells (MSCs) are known to both have powerful immunosuppressive properties and promote allograft tolerance. Determining the environmental oxygen tension and inflammatory conditions under which MSCs are optimally primed for this immunosuppressive function is essential to their utilization in promoting graft tolerance. Of particular interest is the mechanisms governing the interaction between MSCs and regulatory T cells (Tregs), which is relatively unknown. We performed our experiments utilizing rat bone marrow derived MSCs. We observed that priming MSCs in hypoxia promotes maintenance of stem-like characteristics, with greater expression of typical MSC cell-surface markers, increased proliferation, and maintenance of differentiation potential. Addition of autologous MSCs to CD4+/allogeneic endothelial cell (EC) co-culture increases regulatory T cell (Treg) proliferation, which is further enhanced when MSCs are primed in hypoxia. Furthermore, MSC-mediated Treg expansion does not require direct cell-cell contact. The expression of indolamine 2,3-dioxygenase, a mediator of MSC immunomodulation, increases when MSCs are primed in hypoxia, and inhibition of IDO significantly decreases the expansion of Tregs. Priming with inflammatory cytokines IFNγ and TNFα increases also expression of markers associated with MSC immunomodulatory function, but decreases MSC proliferation. The expression of IDO also increases when MSCs are primed with inflammatory cytokines. However, there is no increase in Treg expansion when MSCs are primed with IFNγ, suggesting an alternate mechanism for inflammatory-stimulated MSC immunomodulation. Overall, these results suggest that MSCs primed in hypoxia or inflammatory conditions are optimally primed for immunosuppressive function. These results provide a clearer picture of how to enhance MSC immunomodulation for clinical use.
PMCID:5841747
PMID: 29513756
ISSN: 1932-6203
CID: 2974842
Absence of Rejection in a Facial Allograft Recipient with a Positive Flow Crossmatch 24 Months after Induction with Rabbit Anti-Thymocyte Globulin and Anti-CD20 Monoclonal Antibody
Background/UNASSIGNED:Donor-specific antibodies (DSA) to human leukocyte antigen increase the risk of accelerated rejection and allograft damage and reduce the likelihood of successful transplantation. Patients with full-thickness facial burns may benefit from facial allotransplantation. However, they are at a high risk of developing DSA due to standard features of their acute care. Case Presentation/UNASSIGNED:A 41-year-old male with severe disfigurement from facial burns consented to facial allotransplantation in 2014; panel reactive antibody score was 0%. In August of 2015, a suitable donor was found. Complement-dependent cytotoxicity crossmatch was negative; flow cytometry crossmatch was positive to donor B cells. An induction immunosuppression strategy consisting of rabbit antithymocyte globulin, rituximab, tacrolimus, mycophenolate mofetil (MMF), and methylprednisolone taper was designed. Total face, scalp, eyelid, ears, and skeletal subunit allotransplantation was performed without operative, immunological, or infectious complications. Maintenance immunosuppression consists of tacrolimus, MMF, and prednisone. As of posttransplant month 24, the patient has not developed acute rejection or metabolic or infectious complications. Conclusions/UNASSIGNED:To our knowledge, this is the first report of targeted B cell agents used for induction immunosuppression in skin-containing vascularized composite tissue allotransplantation. A cautious approach is warranted, but early results are promising for reconstructive transplant candidates given the exceptionally high rate of acute rejection episodes, particularly in the first year, in this patient population.
PMCID:5985128
PMID: 29888023
ISSN: 2090-6943
CID: 3154932
Journal of plastic, reconstructive & aesthetic surgery : JPRAS. 2017:70(9):1285-1291.DOI: 10.1016/j.bjps.2017.06.028
How many people work in your operating room? An assessment of factors associated with instrument recounts within plastic surgery
BACKGROUND: Intraoperative instrument recounts are performed to avoid retained foreign surgical items. These additional counts, however, beget risks of their own, including prolonged operative times, exposure to radiation, and increased cost. Our study aimed to identify factors that increase the likelihood of instrument recounts during plastic surgery procedures, and use our findings to guide potential solutions for preventing unnecessary recounts across all surgical fields. STUDY DESIGN: This is a retrospective review of all plastic surgical cases in the main operating setting at New York University Langone Medical Center (NYULMC) between March 2014 and February 2015. RESULTS: Of 1285 plastic surgery cases, 35 (2.7%) reported a missing instrument necessitating a recount. Of all subspecialties within plastic surgery, only microsurgery conferred an increased risk of a recount event. We identified multiple factors that increased the odds of a recount event, including increased operative time, number of surgical sites, and intraoperative instrument handoffs. CONCLUSION: Instrument recounts, although designed to prevent inadvertently retained surgical items, present inherent risks of their own. In a large retrospective review of plastic surgery cases at our medical center, we identified many factors that increased the likelihood of an instrument recount. On the basis of our findings and prior literature, we recommend limiting the number of staff handling instrument, the number of handoffs, and a heightened awareness by surgeons and perioperative staff of specific procedures and factors that increase the risk of a miscount event.
PMID: 28734751
ISSN: 1878-0539
CID: 2654112
Does the Timing of Chemotherapy Affect Post-Mastectomy Breast Reconstruction Complications?
INTRODUCTION: In this study we evaluated how the timing of chemotherapy for breast cancer affects post-reconstruction complications to determine whether there is an optimal time for breast reconstruction after chemotherapy. PATIENTS AND METHODS: A retrospective review identified 344 breast cancer patients who underwent chemotherapy with mastectomy and autologous/prosthetic reconstruction from 2011 to 2014. A control group of 127 breast cancer patients who underwent mastectomy and autologous/prosthetic reconstruction without chemotherapy was also identified from the same period. The 2 groups were compared and analyzed for differences in demographic characteristics, treatment, and postoperative complication rates. The chemotherapy group was subsequently stratified into 3 subgroups on the basis of the number of days between chemotherapy treatment and reconstructive surgery ( 60 days) for further analysis. RESULTS: Patients who received chemotherapy were followed for an average of 803.4 days (26.4 months) from the time of initial reconstruction (mean time to complication, 43.3 +/- 82.7 days), and experienced an overall greater complication rate compared with control subjects (32.8% vs. 24.4%; P = .078). When complications were divided into minor, major, and reconstructive failure categories, analysis revealed that the chemotherapy group experienced more minor complications than the control group (18% vs. 11%; P = .067). However, there were no statistically significant differences in major complication rates (10.5% vs. 9.4%) and reconstructive failure complication rates (3.8% vs. 2.4%) between the chemotherapy group and control group. Sixty-eight patients (19.8%) underwent surgery within 30 days of chemotherapy, 210 patients (61%) within 30 to 60 days, and 66 patients (19.2%) after 60 days. Of note, patients in the 60 days), time to complication, complication severity, or complication type. Whereas patients who underwent surgery 30 to 60 days from the time of chemotherapy had lower rates of skin necrosis (3.8%) and infection (15.7%) compared with the
PMID: 28336245
ISSN: 1938-0666
CID: 2499612
Novel lipoproteoplex delivers Keap1 siRNA based gene therapy to accelerate diabetic wound healing
Therapeutics utilizing siRNA are currently limited by the availability of safe and effective delivery systems. Cutaneous diseases, specifically ones with significant genetic components are ideal candidates for topical siRNA based therapy but the anatomical structure of skin presents a considerable hurdle. Here, we optimized a novel liposome and protein hybrid nanoparticle delivery system for the topical treatment of diabetic wounds with severe oxidative stress. We utilized a cationic lipid nanoparticle (CLN) composed of 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) and the edge activator sodium cholate (NaChol), in a 6:1 ratio of DOTAP:NaChol (DNC). Addition of a cationic engineered supercharged coiled-coil protein (CSP) in a 10:1:1 ratio of DNC:CSP:siRNA produced a stable lipoproteoplex (LPP) nanoparticle, with optimal siRNA complexation, minimal cytotoxicity, and increased transfection efficacy. In a humanized murine diabetic wound healing model, our optimized LPP formulation successfully delivered siRNA targeted against Keap1, key repressor of Nrf2 which is a central regulator of redox mechanisms. Application of LPP complexing siKeap1 restored Nrf2 antioxidant function, accelerated diabetic tissue regeneration, and augmented reduction-oxidation homeostasis in the wound environment. Our topical LPP delivery system can readily be translated into clinical use for the treatment of diabetic wounds and can be extended to other cutaneous diseases with genetic components.
PMID: 28391065
ISSN: 1878-5905
CID: 2528042
Impact of Evolving Radiation Therapy Techniques on Implant-Based Breast Reconstruction
BACKGROUND: Patients undergoing implant-based reconstruction in the setting of postmastectomy radiation therapy suffer from increased complications and inferior outcomes compared with those not irradiated, but advances in radiation delivery have allowed for more nuanced therapy. The authors investigated whether these advances impact patient outcomes in implant-based breast reconstruction. METHODS: Retrospective chart review identified all implant-based reconstructions performed at a single institution from November of 2010 to November of 2013. These data were cross-referenced with a registry of patients undergoing breast irradiation. Patient demographics, treatment characteristics, and outcomes were analyzed. RESULTS: Three hundred twenty-six patients (533 reconstructions) were not irradiated, whereas 83 patients (125 reconstructions) received radiation therapy; mean follow-up was 24.7 months versus 26.0 months (p = 0.49). Overall complication rates were higher in the irradiated group (35.2 percent versus 14.4 percent; p < 0.01). Increased maximum radiation doses to the skin were associated with complications (maximum dose to skin, p = 0.05; maximum dose to 1 cc of skin, p = 0.01). Different treatment modalities (e.g., three-dimensional conformal, intensity-modulated, field-in-field, and hybrid techniques) did not impact complication rates. Prone versus supine positioning significantly decreased the maximum skin dose (58.5 Gy versus 61.7 Gy; p = 0.05), although this did not translate to significantly decreased complication rates in analysis of prone versus supine positioning. CONCLUSIONS: As radiation techniques evolve, the maximum dose to skin should be given consideration similar to that for heart and lung dosing, to optimize reconstructive outcomes. Prone positioning significantly decreases the maximum skin dose and trends toward significance in reducing reconstructive complications. With continued study, this may become clinically important. Interdepartmental studies such as this one ensure quality of care. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.
PMID: 28538549
ISSN: 1529-4242
CID: 2574862
The Nrf2/Keap1/ARE Pathway and Oxidative Stress as a Therapeutic Target in Type II Diabetes Mellitus
Despite improvements in awareness and treatment of type II diabetes mellitus (TIIDM), this disease remains a major source of morbidity and mortality worldwide, and prevalence continues to rise. Oxidative damage caused by free radicals has long been known to contribute to the pathogenesis and progression of TIIDM and its complications. Only recently, however, has the role of the Nrf2/Keap1/ARE master antioxidant pathway in diabetic dysfunction begun to be elucidated. There is accumulating evidence that this pathway is implicated in diabetic damage to the pancreas, heart, and skin, among other cell types and tissues. Animal studies and clinical trials have shown promising results suggesting that activation of this pathway can delay or reverse some of these impairments in TIIDM. In this review, we outline the role of oxidative damage and the Nrf2/Keap1/ARE pathway in TIIDM, focusing on current and future efforts to utilize this relationship as a therapeutic target for prevention, prognosis, and treatment of TIID.
PMCID:5585663
PMID: 28913364
ISSN: 2314-6753
CID: 2701332
Total Face, Eyelids, Ears, Scalp, and Skeletal Subunit Transplant: A Reconstructive Solution for the Full Face and Total Scalp Burn
BACKGROUND: Reconstruction of extensive facial and scalp burns can be increasingly challenging, especially in patients that have undergone multiple procedures with less than ideal outcomes resulting in restricting neck and oral contractures, eyelid dysfunction, and suboptimal aesthetic appearance. METHODS: To establish a reconstructive solution for this challenging deformity, a multidisciplinary team was assembled to develop the foundation to a facial vascularized composite allotransplantation program. The strategy of developing and executing a clinical transplant was derived on the basis of fostering a cohesive and supportive institutional clinical environment, implementing computer software and advanced technology, establishing a cadaveric transplant model, performing a research facial procurement, and selecting an optimal candidate with the aforementioned burn defect who was well informed and had the desire to undergo face transplantation. RESULTS: Approval from the institutional review board and organ procurement organization enabled our face transplant team to successfully perform a total face, eyelids, ears, scalp, and skeletal subunit transplant in a 41-year-old man with a full face and total scalp burn. CONCLUSIONS: The culmination of knowledge attained from previous experiences continues to influence the progression of facial vascularized composite allotransplantation. This surgical endeavor methodically and effectively synchronized the fundamental principles of aesthetic, craniofacial, and microvascular surgery to restore appearance and function to a patient suffering from failed conventional surgery for full face and total scalp burns. This procedure represents the most extensive soft-tissue clinical face transplant performed to date. CLINICAL QUESTION/LEVEL OF EVIDEMCE: Therapeutic, V.
PMID: 27348652
ISSN: 1529-4242
CID: 2165512
Total Face, Eyelids, Ears, Scalp, and Skeletal Subunit Transplant Cadaver Simulation: The Culmination of Aesthetic, Craniofacial, and Microsurgery Principles
BACKGROUND: The application of aesthetic, craniofacial, and microsurgical principles in the execution of face transplantation may improve outcomes. Optimal soft-tissue face transplantation can be achieved by incorporating subunit facial skeletal replacement and subsequent tissue resuspension. The purpose of this study was to establish a reconstructive solution for a full face and scalp burn and to evaluate outcome precision and consistency. METHODS: Seven mock face transplants (14 cadavers) were completed in the span of 1 year. Components of the vascularized composite allograft included the eyelids, nose, lips, facial muscles, oral mucosa, total scalp, and ears; and skeletal subunits of the zygoma, nasal bone, and genial segment. Virtual surgical planning was used for osteotomy selection, and to evaluate postoperative precision of hard- and soft-tissue elements. RESULTS: Each transplant experience decreased each subsequent transplant surgical time. Prefabricated cutting guides facilitated a faster dissection of both donor and recipient tissue, requiring minimal alteration to the allograft for proper fixation of bony segments during inset. Regardless of donor-to-recipient size discrepancy, ample soft tissue was available to achieve tension-free allograft inset. Differences between virtual transplant simulation and posttransplant measurements were minimal or insignificant, supporting replicable and precise outcomes. CONCLUSIONS: This facial transplant model was designed to optimize reconstruction of extensive soft-tissue defects of the craniofacial region representative of electrical, thermal, and chemical burns, by incorporating skeletal subunits within the allograft. The implementation of aesthetic, craniofacial, and microsurgical principles and computer-assisted technology improves surgical precision, decreases operative time, and may optimize function.
PMID: 27119930
ISSN: 1529-4242
CID: 2092072
