A machine learning analysis of patient concerns regarding mastopexy.

BACKGROUND: Social media plays an important role in connecting patients and plastic surgeons. We utilized patient inquiries regarding mastopexy from an online social media site to determine the most prevalent patient concerns, while employing a machine-learning algorithm to generate the questions representative of the dataset. OBJECTIVE: This data allow plastic surgeons to better tailor their preoperative consultations to address common concerns, set realistic expectations, and improve overall satisfaction. METHODS: A total of 2,011 inquiries from the mastopexy section of Realself.com were obtained using an open-source web crawler. Each inquiry was manually categorized as preoperative or postoperative and classified into subcategories based upon the free text entry. Lastly, questions were analyzed using machine learning to determine ten questions most representative of the inquiry pool. RESULTS: Of the 2,011 inquiries analyzed, 52.91% were preoperative and 47.09% were postoperative. Most preoperative questions asked about procedure eligibility (309, 29.04%), surgical techniques and logistics (260, 24.44%), and the best type of breast lift for the user (259, 24.34%). Among postoperative questions, questions regarding appearance were the most common (491, 51.85%), followed by symptoms after surgery (197, 19.75%) and behavior allowed/disallowed (145, 15.31%). Appearance was further subcategorized with the most common categories being appearance of the nipple (98, 19.86%), skin discoloration (88, 17.92%), and scarring (74, 15.07%). CONCLUSION: By utilizing the data that social media websites, like Realself.com, provide, plastic surgeons can better understand common patient concerns. This data aid in optimizing the preoperative consultation process to address the common concerns, recalibrate unrealistic expectations, and improve overall satisfaction.

Tolerance of a Vascularized Composite Allograft Achieved in MHC Class-I-mismatch Swine via Mixed Chimerism.

Background: Vascularized composite allografts (VCAs) allow reconstruction of devastating injuries and amputations, yet require lifelong immunosuppression that is associated with significant morbidity. Induction of immune tolerance of VCAs would permit widespread use of these procedures. VCAs are acquired from deceased donors most likely to be fully-MHC-mismatched (in contrast to living-related renal transplant donor-recipient pairs matched at one MHC haplotype). After achieving VCA tolerance in a swine model equivalent to clinical living-related renal transplants (single-haplotype MHC mismatches: e.g., "mother-daughter"/haploidentical), we tested our protocol in MHC class I, class II, and fully-MHC-mismatched pairs. Although class II mismatched swine demonstrated similar results as the haploidentical scenario (stable mixed chimerism and tolerance), our protocol failed to prevent rejection of class I and full mismatch VCAs. Here, we describe a new adapted conditioning protocol that successfully achieved tolerance across MHC class-I-mismatch barriers in swine. Methods: Swine were treated with non-myeloablative total body and thymic irradiation two days prior to infusion of bone marrow cells from an MHC class I-mismatched donor. They also received a short-term treatment with CTLA4-Ig (Belatacept®) and anti-IL6R mAb (Tociluzimab®) and were transplanted with an osteomyocutaneous VCA from the same donor. Results: Stable mixed chimerism and tolerance of MHC class-I-mismatched VCAs was achieved in 3 recipients. Allograft tolerance was associated with a sustained lack of anti-donor T cell response and a concomitant expansion of double negative CD4-CD8- T cells producing IL-10. Conclusions: This study demonstrates the first successful mixed chimerism-induced VCA tolerance in a large animal model across a MHC class-I-mismatch. Future studies aimed at fully-mismatched donor-recipient pairs are under investigation with this protocol.

Local Immunosuppression for Vascularized Composite Allografts: Application of Topical FK506-TyroSpheres in a Nonhuman Primate Model.

Transplantation of vascularized composite allografts (VCAs) provides a means of restoring complex anatomical and functional units following burns and other disfigurement otherwise not amenable to conventional autologous reconstructive surgery. While short- to intermediate-term VCA survival is largely dependent on patient compliance with medication, the myriad of side effects resulting from lifelong systemic immunosuppression continue to pose a significant challenge. Topical immunosuppression is therefore a logical and attractive alternative for VCA. Current formulations are limited though, by poor skin penetration but this may be mitigated by conjugation of immunosuppressive drugs to TyroSpheres for enhanced delivery. Therefore, we investigated the topical application of FK506-TyroSpheres (in the form of a gel dressing) in a clinically relevant nonhuman primate VCA model to determine if allograft survival could be prolonged at reduced levels of maintenance systemic immunosuppression. Six Major Histocompatibility Complex (MHC)-mismatched cynomolgus macaques (Macaca fascicularis) served as reciprocal donors and recipients of radial forearm fasciocutaneous flaps. Standard Bacitracin ointment and FK506-TyroSpheres were applied every other day to the VCAs of animals in groups 1 (controls, n = 2) and 2 (experimental, n = 4), respectively, before gradual taper of systemic FK506. Clinical features of VCA rejection still developed when systemic FK506 fell below 10 ng/ml despite application of FK506-TyroSpheres and prolonged VCA survival was not achieved. However, unwanted systemic FK506 absorption was avoided with TyroSphere technology. Further refinement to optimize local drug delivery profiles to achieve and maintain therapeutic delivery of FK506 with TyroSpheres is underway, leveraging significant experience in controlled drug delivery to mitigate acute rejection of VCAs.

Toward Development of the Delayed Tolerance Induction Protocol for Vascularized Composite Allografts in Nonhuman Primates.

BACKGROUND: Transplantation of vascularized composite allografts is limited mainly by the need for life-long immunosuppression. The consequent side effects and looming specter of chronic rejection portend eventual allograft loss. Development of tolerogenic protocols is thus of utmost importance to the field of vascularized composite allograft transplantation. METHODS: With a modified delayed tolerance induction protocol, 10 cynomolgus macaques received hand (n = 2) or face vascularized composite allografts across both full and haploidentical major histocompatibility complex barriers before donor bone marrow transplantation at a later date. Protocol and for-cause allograft skin biopsies were performed for immunohistochemical analysis and analysis of donor-recipient leukocyte contribution; mixed chimerism in peripheral blood and in vitro immune responses were assessed serially. RESULTS: Before bone marrow transplantation, maintenance immunosuppression for 4 months led to lethal complications, including posttransplant lymphoproliferative disorder (in two of four recipients), which necessitated early study termination. Shortening the maintenance period to 2 months was clinically relevant and allowed all subsequent subjects (n = 6) to complete the delayed tolerance induction protocol. Acute rejection developed within the first 2 to 4 weeks after transplantation, with corresponding near-complete turnover of allograft leukocytes from donor to recipient origin, but donor-specific antibodies remained negative. After bone marrow transplantation, mixed chimerism failed to develop, although carboxyfluorescein succinimidyl ester mixed lymphocyte reaction demonstrated generalized unresponsiveness. However, the accrual of subsequent rejection episodes eventually culminated in graft vasculopathy and irreversible allograft loss. CONCLUSIONS: Despite the various advantages of the delayed tolerance induction protocol, it failed to reliably induce mixed chimerism and thus immunologic tolerance to vascularized composite allografts, given currently available immunosuppression treatment options. Ongoing work shows promise in overcoming these limitations.

Clinical Impact of Cryopreservation on Split Thickness Skin Grafts in the Porcine Model.

Vital, genetically engineered, porcine xenografts represent a promising alternative to human cadaveric allografts (HCA) in the treatment of severe burns. However, their clinical value would be significantly enhanced if preservation and long-term storage-without the loss of cellular viability-were feasible. The objective of this study was to examine the direct impact of cryopreservation and the length of storage on critical in vivo and in vitro parameters, necessary for a successful, potentially equivalent substitute to HCA. In this study, vital, porcine skin grafts, continuously cryopreserved for more than 7 years were compared side-by-side to otherwise identically prepared skin grafts stored for only 15 minutes. Two major histocompatibility complex (MHC)-controlled donor-recipient pairs received surgically created deep-partial wounds and subsequent grafting with split-thickness porcine skin grafts, differentiated only by the duration of storage. Clinical and histological outcomes, as well as quantification of cellular viability via a series of 3-4,5-dimethylthiazol-2-yl]-2,5 diphenyltetrazolium bromide (MTT) assays, were assessed. No statistically significant differences were observed between skin grafts cryopreserved for 15 minutes vs 7 years. Parametric distinctions between xenografts stored for short- vs long-term durations could not be ascertained across independent clinical, histological, or in vitro evaluative methods. The results of this study validate the ability to reliably preserve, store, and retain the essential metabolic activity of porcine tissues after cryopreservation. Plentiful, safe, and readily accessible inventories of vital xenografts represent an advantageous solution to numerous limitations associated with HCA, in the treatment of severe burns.

Graft vasculopathy of vascularized composite allografts in humans: a literature review and retrospective study.

Mechanisms of chronic rejection of vascularized composite allografts (VCA) remain poorly understood and likely present along a spectrum of highly varied clinicopathological findings. Across both animal and human VCA however, graft vasculopathy (GV) has been the most consistent pathological finding resulting clinically in irreversible allograft dysfunction and eventual loss. A literature review of all reported clinical VCA cases with documented GV up to December 2018 was thus performed to elucidate the possible mechanisms involved. Relevant data extracted include C4d deposition, donor-specific antibody (DSA) formation, extent of human leukocyte antigen (HLA) mismatch, pretransplant panel reactive antibody levels, induction and maintenance immunosuppression used, the number of preceding acute rejection episodes, and time to histological confirmation of GV. Approximately 6% (13 of 205) of all VCA patients reported to date developed GV at a mean of 6 years post-transplantation. 46% of these patients have either lost or had their VCAs removed. Neither C4d nor DSA alone was predictive of GV development; however, when both are present, VCA loss appears inevitable due to progressive GV. Of utmost concern, GV in VCA does not appear to be abrogated by currently available immunosuppressive treatment and is essentially irreversible by the time of diagnosis with allograft loss a likely eventuality.

Dermabrasion and Thin Epidermal Grafting for Treatment of Large and Small Areas of Postburn Leukoderma: A Case Series and Review of the Literature.

Deep burn injuries can have serious aesthetic consequences as it often results in scar tissue and pigmentary changes of the skin. The focus of this article is to report our experience and results using dermabrasion and thin split-thickness skin grafting as a technique for restoring skin pigmentation after burn injuries. Patient records were obtained from a pediatric burn hospital medical record database from 1990 to 2007. Both charts and photographs were retrospectively reviewed. The treatment was evaluated for body region treated, surface area involved, effectiveness of treatment, and number of treatments required. Indications for the procedure included longstanding depigmentation, defined as greater than 1 year, and a patient wiling to have a donor site. The areas of vitiligo were marked and dermabraded with a mechanical dermabrader. Thin epidermal grafts with a thickness of 6 thousands of an inch were harvested with an air-powered dermatome. The grafts were affixed to the dermabraded bed and dressed open or with nonstick gauze for areas of the face and wrapped for areas in the extremities. Eleven patients underwent 16 procedures. The average size of the graft per procedure was 87 cm (4-500 cm). All results were consistent and long-lasting at follow-up. Postburn leukoderma of long duration is well treated by dermabrasion and thin split-thickness skin grafting. This study is unique in describing grafting on multiple occasions and for larger areas than previously described, with two patients undergoing grafting more than 200 cm.