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Reducing complications while controlling costs is a central tenet of value-based health care. Bilateral microvascular breast reconstruction is a long operation with a relatively high complication rate. Using a two-surgeon team has been shown to improve safety in bilateral microvascular breast reconstruction; however, its impact on cost and efficiency has not been robustly studied. The authors hypothesized that a cosurgeon for bilateral microvascular breast reconstruction is safe, effective, and associated with reduced costs.The authors retrospectively reviewed all patients who underwent bilateral microvascular breast reconstruction with either a single surgeon or surgeon/cosurgeon team over an 18-month period. Charges were converted to costs using the authors' institutional cost-to-charge ratio. Surgeon opportunity costs were estimated using time-driven activity-based costing. Propensity scoring controlled for baseline characteristics between the two groups. A locally weighted logistic regression model analyzed the cosurgeon's impact on outcomes and costs.The authors included 150 bilateral microvascular breast reconstructions (60 single-surgeon and 90 surgeon/cosurgeon reconstructions) with a median follow-up of 15 months. After matching, the presence of a cosurgeon was associated with a significantly reduced mean operative duration (change in operative duration, -107 minutes; p0.001) and cost (change in total cost, -$1101.50; p0.001), which was even more pronounced when surgeon/cosurgeon teams worked together frequently (change in operative duration, -132 minutes; change in total cost, -$1389; p = 0.007). The weighted logistic regression models identified that a cosurgeon was protective against breast-site complications and trended toward reduced overall and major complication rates.The practice of using a of cosurgeon appears to be associated with reduced costs and improved outcomes, thereby potentially adding value to bilateral microvascular breast reconstruction.Therapeutic, III.

BACKGROUND Traumatic amputation is the second leading cause of limb loss in the United States. The preferred treatment is salvage and replantation of the amputated limb, whenever possible, and allotransplantation is a novel procedure whereby healthy limbs are procured from deceased organ donors and transplanted into the amputee recipient. A major restriction for both procedures is the irrecoverable muscle damage occurring due to ischemia. We investigated the feasibility of using a novel lightweight, mobile perfusion device specifically designed to perfuse amputated porcine limbs with an acellular perfusion solution to delay ischemic muscle damage prior to transplantation or replantation. METHODS Bilateral hind limbs of Yorkshire pigs were amputated; one of the limbs was preserved by perfusion in the mobile perfusion device, and the other by storage in ice slurry for 12 hours. RESULTS Five sets of bilateral limbs were preserved as described previously. A defined pressure of 30 mm Hg was reliably maintained in the arterial system without loss of flow. Comparison of the perfusate composition before and after limb passage revealed significant differences. Muscle biopsies showed a consistent progression of clusters of hypoxic cells in the control limbs with time. Similar changes could not be observed in the perfused tissue. CONCLUSIONS We have designed and built a small, mobile perfusion device that is operational and that more closely mimics the normal physiological environment when compared with the current standard of preservation in ice slurry. This project may have far-reaching implications for the treatment of limb loss through replantation and transplantation.

Since the first successful hand transplantation in 1998, 72 patients have been operated on for unilateral/bilateral hand transplantation across 13 countries. There have been multiple studies evaluating the outcomes of hand transplantation; however, there is considerable variability among the outcome measures evaluated in these studies.This article reports functional outcomes in a patient with bilateral hand transplants at a mid-forearm level with serial follow-ups over 3.5 years. Different parameters used to study the functional outcomes include the Disabilities of the Arm, Shoulder, and Hand score, the Carroll test, the Hand Transplant Score System, the Short Form-36 Health Survey, and routine occupational therapy measures. Various task-oriented outcomes were also assigned to provide milestones to the recovery.The patient had a Disabilities of the Arm, Shoulder, and Hand score of 40, a Carroll test score of 48 (right) and 49 (left), and a Hand Transplant Score System score of 58 (right) and 57.5 (left) at 3.5-year follow-up. Interestingly, his objective scores did not change significantly during the follow-up, but he continued to function quite independently and is subjectively pleased with his outcomes.Multiple functional outcome measures provide an objective way to follow patients who have undergone hand transplantation. The authors propose a series of measures to elucidate subtleties in functional gains. However, use of this series in isolation may belie subjectively good results. They also propose a series of milestones in the recovery to give a better real-world explanation of progress.Therapeutic, V.

Current immunosuppression in VCA is largely based on the experience in solid organ transplantation. It remains unclear if steroids can be reduced safely in VCA recipients. We report on five VCA recipients who were weaned off maintenance steroids after a median of 2 months (mean: 4.8 months, range 2-12 months). Patients were kept subsequently on a low dose, dual maintenance consisting of tacrolimus and mycophenolate mofetil/mycophenloic acid with a mean follow-up of 43.6 months (median = 40 months, range 34-64 months). Early and late acute rejections responded well to temporarily augmented maintenance, topical immunosuppression, and/or steroid bolus treatment. One late steroid-resistant acute rejection required treatment with thymoglobulin. All patients have been gradually weaned off steroids subsequent to the treatment of acute rejections. Low levels of tacrolimus (

Transplantation of skin micrografts in a 1:100 ratio regenerate the epidermis of full-thickness wounds in pigs within 14 days in a wet environment. The aim of the current study was to combine micrografts and commercially available moist dressings. We hypothesized that micrografts regenerate the epidermis when covered with a moist dressing. 5cm×5cm and 10cm×10cm full-thickness wounds were created on the backs of pigs. Wounds were transplanted with 0.8mm×0.8mm micrografts created from a split-thickness skin graft in a 1:100 ratio. 5cm×5cm wounds were treated with wound chambers, moist dressings or dry gauze (non-transplanted control group). 10cm×10cm wounds were compared to non-transplanted wounds, both covered with moist dressings. Reepithelialization was assessed in biopsies from day 10, 14 and 18 post-transplantation. 5cm×5cm transplanted wounds covered with moist dressings showed 69.5±20.6% reepithelialization by day 14 and 90.5±10.4% by day 18, similar to wounds covered with a wound chamber (63.9±16.7 and 86.2±11.9%, respectively). 18 days post-transplantation, 10cm×10cm transplanted wounds covered with moist dressings showed 66.1±10.3% reepithelialization, whereas nontransplanted wounds covered with moist dressings were 40.6±6.6% reepithelialized. We conclude that micrografts combined with clinically available moist dressings regenerate the epidermis of full-thickness wounds.

The vascular reorganization after facial transplantation has important implications on future surgical planning. The purpose of this study was to evaluate blood flow (BF) after full face transplantation using wide area-detector computed tomography (CT) techniques. Three subjects with severe craniofacial injury who underwent full face transplantation were included. All subjects underwent a single anastomosis bilaterally of the artery and vein, and the recipient tongue was preserved. Before and after surgery, dynamic volume CT studies were analyzed for vascular anatomy and blood perfusion. Postsurgical CT showed extensive vascular reorganization for external carotid artery (ECA) angiosome; collateral flows from vertebral, ascending pharyngeal or maxillary arteries supplied the branches from the recipient ECAs distal to the ligation. While allograft tissue was slightly less perfused when the facial artery was the only donor artery when compared to an ECA-ECA anastomosis (4.4 ± 0.4% vs. 5.7 ± 0.7%), allograft perfusion was higher than the recipient normal neck tissue. BF for the recipient tongue was maintained from contralateral/donor arteries when the lingual artery was sacrificed. Venous drainage was adequate for all subjects, even when the recipient internal jugular vein was anastomosed in end-to-end fashion on one side. In conclusion, dynamic CT identified adequate BF for facial allografts via extensive vascular reorganization.

BACKGROUND Face transplantation can provide improved quality of life to severely disfigured individuals. The unique challenges of face transplantation prompted much ethical discussion even before the first clinical case. Many deemed it unethical, because of issues ranging from the need for potentially harmful immunosuppression to the potential transfer of identity. Over time, the ethical debate surrounding face transplantation has evolved. METHODS In August of 2012, the authors performed a review of the scientific literature on the ethics of face transplantation, focusing on the evolution of the discussion from before to after the first clinical case in 2005. The authors conducted a primary search (73 peer-reviewed publications) in PubMed using combinations of the terms "ethics" and "face transplantation" and "opinions," and a secondary search (37 peer-reviewed publications) retrieving publications cited in some of the primary search findings. In total, the authors reviewed 110 articles. RESULTS A series of 15 issues were addressed repeatedly throughout the reviewed articles. The authors observed an evolution of the general opinion regarding face transplantation: initially seen almost unanimously as an outlandish and morally objectionable procedure, it began to be accepted as a feasible and necessary treatment option for the most significant facial defects. CONCLUSION With growing clinical experience globally, new ethical questions have arisen that must be addressed to move the field of face transplantation forward in an ethically sound manner.

Background Hand allotransplantation can restore motor, sensory and cosmetic functions to upper extremity amputees. Over 70 hand transplant operations have been performed worldwide, but there is little published regarding post-hand transplant rehabilitation. Methods The Brigham and Women's Hospital (BWH) Hand Transplantation Team's post-hand transplant rehabilitation protocol is presented here. The protocol must be modified to address each transplant recipient's unique needs. It builds on universally used modalities of hand rehabilitation such as splinting, edema and scar management, range of motion exercises, activities of daily living training, electrical stimulation, cognitive training and strengthening. Results The BWH hand transplant rehabilitation protocol consists of four phases with distinct goals, frequency, and modalities. (1) Pre-operative: functional assessments are completed and goals and expectations of transplantation are established. (2) Initial post-operative (post-operative weeks 1–2): hand protection, minimization of swelling, education, and discharge. (3) Intermediate (post-operative weeks 2–8): therapy aims to prevent and/or decrease scar adhesion, increase tensile strength, flexibility and function, and prevent joint contractures. (4) Late (from 8 weeks forward): maximization of function and strength, and transition to routine activities. The frequency of rehabilitation therapy decreases gradually from the initial to late phases. Conclusions Rehabilitation therapy after hand transplantation follows a progressive increase in activity in parallel with wound healing and nerve regeneration. Careful documentation of progress and outcomes is essential to demonstrate the utility of interventions and to optimize therapy protocols.

For many living with the devastating aftermath of disfiguring facial injuries, extremity amputations, and other composite tissues defects, conventional reconstruction offers limited relief. Full restoration of the face or extremities with anatomic equivalents recently became possible with decades of advancements in transplantation and regenerative medicine. Vascularized composite allotransplantation (VCA) is the transfer of anatomic equivalents from immunologically and aesthetically compatible donors to recipients with severe defects. The transplanted tissues are "composite" because they include multiple types essential for function, for example, skin, muscle, nerves, and blood vessels. More than 100 patients worldwide have benefited from VCA, the majority receiving hand or face transplants. Despite its demonstrated results, the clinical practice of VCA is limited by center experience, public awareness, donor shortage, and the risks of lifelong immune suppression. Tissue engineering (TE) is the generation of customized tissues in the laboratory using cells, biomaterials and bioreactors. Tissue engineering may eventually supersede VCA in the clinic, because it bypasses donor shortage and immune suppression challenges. Billions of dollars have been invested in TE research and development, which are expected to result in a myriad of clinical products within the mid- to long-term. First, tissue engineers must address challenges such as vascularization of engineered tissues and maintenance of phenotype in culture. If these hurdles can be overcome, it is to be hoped that the lessons learned through decades of research in both VCA and TE will act synergistically to generate off-the-shelf composite tissues that can thrive after implantation and in the absence of immune suppression.

Full face transplantation raises a new set of ethical concerns and technical difficulties when compared with partial face transplantation. Previously, it was thought that full face allografts must include bilateral superficial temporal and facial arteries, dictating the need for inclusion of donor parotid glands. This would lead to poor aesthetic outcomes and limit facial nerve coaptation to the level of the main trunk, which often results in synkinesias. The authors present a new approach to full facial allograft recovery based on blood supply from facial arteries alone. This approach eliminates the need to include parotid glands, enabling more distal coaptation of facial nerve branches and targeted innervation of effector muscles. The recovery can be reproducibly performed within 4 hours.Three mock cadaver dissections and three full face transplantations were performed.Donor facial allografts were dissected in cranio-caudal and lateral-to-medial fashion. Individual facial nerve branches were cut medial to parotid glands and coapted to corresponding recipient nerve branches. With the exception of one parotid gland used to add bulk, parotids were generally not included in the allografts. Relevant sensory nerves were coapted. External carotid arteries were dissected, leaving only bilateral facial arteries as the primary arterial supply. All full facial allografts were well perfused immediately following transplantation and are surviving.The authors describe a new, simple, and reproducible technique of full facial allograft recovery that allows perfusion using only bilateral facial arteries. Their technique follows critical principles of targeted sensory and motor nerve coaptation.

Aphids exhibit divergent modes of embryogenesis during the sexual and asexual phases of the life cycle. To explore how a single genome can give rise to these alternative developmental modes, we have initiated embryological studies of the pea aphid, Acyrthosiphon pisum. Here we present a detailed description of parthenogenetic, viviparous embryonic development in the pea aphid. We compare and contrast development of the parthenogenetic embryo with that of the embryo resulting from sexual reproduction. The primary difference between the embryos is the scale on which development occurs: early parthenogenetic development occurs in a volume approximately three orders of magnitude smaller than the sexual egg, largely because of the apparent absence of yolk in the parthenogenetic egg. This results in a drastically different duration of syncytial energid cleavage and, presumably, patterning processes in the two embryos must act at scales that differ by orders of magnitude. The eggs also develop on time scales that differ approximately by an order of magnitude and the timing of the embryonic movements, collectively called blastokinesis, have temporally shifted relative to growth of the embryo. In addition, the endosymbiotic bacteria are transferred from mother to embryo in different ways in the two embryos. Finally, the function of the serosa has diverged greatly in the two embryos: in the sexual egg the serosa deposits a thick cuticle that protects the egg, whereas the serosa of the parthenogenetic embryo is greatly reduced and its function is unclear. The pea aphid is a useful model system for examining how a single genome has evolved to allow divergent modes of development.

Facial allotransplantation is a revolutionary operation that has at last introduced the possibility of nearly normal facial restoration to patients afflicted by the most severe cases of facial disfigurement.The facial transplantation team at Brigham and Women's Hospital evaluated more than 20 patients as potential face transplant recipients; of these, six became face transplant candidates and underwent full screening procedures. The team performed facial allotransplantations in four of these patients between April of 2009 and May of 2011. This is the largest clinical volume of facial transplant recipients in the United States to date.The authors have learned important lessons from each of these four unique cases and from the more than 20 patients that they have evaluated as potential face transplant recipients. The authors have translated lessons learned through direct experience into a set of fundamental surgical principles of the operation.The authors' surgical principles emphasize safety, technical feasibility, preservation of functional facial units, and return of motor and sensory function. This article describes each of these principles along with their rationale and, in some instances, illustrates their application.

Achieving significant adhesion to soft tissues while minimizing tissue damage poses a considerable clinical challenge. Chemical-based adhesives require tissue-specific reactive chemistry, typically inducing a significant inflammatory response. Staples are fraught with limitations including high-localized tissue stress and increased risk of infection, and nerve and blood vessel damage. Here inspired by the endoparasite Pomphorhynchus laevis, which swells its proboscis to attach to its host's intestinal wall, we have developed a biphasic microneedle array that mechanically interlocks with tissue through swellable microneedle tips, achieving ~3.5-fold increase in adhesion strength compared with staples in skin graft fixation, and removal force of ~4.5 N cm(-2) from intestinal mucosal tissue. Comprising a poly(styrene)-block-poly(acrylic acid) swellable tip and non-swellable polystyrene core, conical microneedles penetrate tissue with minimal insertion force and depth, yet high adhesion strength in their swollen state. Uniquely, this design provides universal soft tissue adhesion with minimal damage, less traumatic removal, reduced risk of infection and delivery of bioactive therapeutics.

Vascularized composite tissue allotransplantation is a viable treatment option for injuries and defects that involve multiple layers of functional tissue. In the past 15 yr, more than 150 vascularized composite allotransplantation (VCA) surgeries have been reported for various anatomic locations including – but not limited to – trachea, larynx, abdominal wall, face, and upper and lower extremities. VCA can achieve a level of esthetic and functional restoration that is currently unattainable using conventional reconstructive techniques. Although the risks of lifelong immunosuppression continue to be an important factor when evaluating the benefits of VCA, reported short- and long-term outcomes have been excellent, thus far. Acute rejections are common in the early post-operative period, and immunosuppression-related side effects have been manageable. A multidisciplinary approach to the management of VCA has proven successful. Reports of long-term graft losses have been rare, while several factors may play a role in the pathophysiology of chronic graft deterioration in VCA. Alternative approaches to immunosuppression such as cellular therapies and immunomodulation hold promise, although their role is so far not defined. Experimental protocols for VCA are currently being explored. Moving forward, it will be exciting to see whether VCA-specific aspects of allorecognition and immune responses will be able to help facilitate tolerance induction.

Objective: Screening for full face transplantation candidates includes computed tomographic vascular mapping of the external carotid distribution for potential arterial and venous anastomoses. The purpose of this study is to illustrate the benefits and drawbacks of cine computed tomographic imaging for preoperative vascular mapping compared with best arterial and venous phase static images. Methods: Two image data sets were retrospectively created and compared for diagnostic findings. The first set of images was the clinical cine computed tomographic acquisition including all phases. The second set of images was composed of the best arterial and best venous phases extracted from the cine loop and determined by the quality of contrast enhancement. For each patient, the benefits and drawbacks of the cine loop were documented in consensus by a plastic surgeon and a radiologist. Results: Cine loop analysis identified retrograde arterial filling not illustrated on the static images alone. Cine assessment identified most of the major vessels necessary for surgery, whereas the static images depicted small vessels more clearly, particularly in the crowded vessel takeoffs. Conclusions: Cine computed tomographic images provide data on direction of blood flow, which is important for preoperative planning. Combination of cine computed tomographic and the best static images will allow comprehensive vascular assessment necessary for future successful full face transplantation.

Summary Introduction Long term follow-up of face transplant patients is fundamental to our understanding of risks and benefits of this procedure. Worldwide experience has shown that function improves gradually over time. Methods In April of 2009, a multidisciplinary team at Brigham and Women's Hospital performed face transplantation on a male patient to address a severe facial defect caused by high-voltage burns. Physical and occupational therapy was performed for the first six post-operative months. Close monitoring of the patient's functional recovery, immunosuppression, and quality of life was performed at set time points. Results Three years after face transplantation, the patient has recovered near-normal sensation. Along with satisfactory aesthetic results, his motor function continues to improve, aiding his speech, facial expressions, and social interaction. Furthermore, the patient reports continued improvements in quality of life. Infectious, metabolic, and immunologic complications have been successfully managed in a team approach. Immunosuppression doses have been effectively reduced, and steroid therapy was withdrawn before the end of the first postoperative year. Conclusions The presented outcomes demonstrate the procedure's growing role in reconstructive surgery as teams continue to focus their efforts on further optimization of immunosuppression and surgical technique.

Objective: Face transplantation replaces substantial defects with anatomically identical donor tissues; preoperative vascular assessment relies on noninvasive imaging to separate and characterize the external carotid vessels and branches. The objective is to describe and illustrate vascular considerations for face transplantation candidates. Methods: Novel noninvasive imaging using computed tomography and magnetic resonance imaging over 3 spatial dimensions plus time was developed and tested in 4 face transplant candidates. Precontrast images assessed bones and underlying metal. Contrast media was used to delineate and separate arteries from veins. For computed tomography, acquisition over multiple time points enabled the computation of tissue perfusion metrics. Time-resolved magnetic resonance angiography was performed to separate arterial and venous phases. Results: The range of circulation times for the external carotid system was 6 to 14 seconds from arterial blush to loss of venous enhancement. Precontrast imaging provided a roadmap of bones and metal. Among the 4 patients, 3 had surgical clips, metal implants, or both within 1 cm of major vessels considered for surgery. Contrast-enhanced wide area detector computed tomographic data acquired in the axial mode separated these structures and provided arterial and venous images for planning the surgical anastomoses. Magnetic resonance imaging was able to distinguish between the large vessels from the external carotid systems. Conclusions: Vascular imaging maps are challenging in face transplantation because of the rapid circulation times and artifact from the initial injury, prior reconstructive attempts, or both. Nevertheless, face transplant candidates require high spatial and temporal resolution vascular imaging to determine those vessels appropriate for surgical anastomoses.

Background: Since the first successful hand transplantation in 1998, there have been multiple reports about surgical technique, transplant survival, and immunosuppression. However, very limited published data exist on psychosocial outcomes following hand transplantation. Methods: We report psychosocial outcomes in a patient with bilateral hand transplants at the midforearm level with serial follow-ups over 3.5 years. Different metrics used to study psychosocial outcomes included the following: SF-12, CES-D, Dyadic Adjustment Scale, Rosenberg SE, and EQ-5D. Result: Preoperatively, our patient did not have any evidence of depression (CES-D = 3), had a nonstressful relationship with his spouse (Dyadic Adjustment Scale = 100), and self-esteem was in the normal range (Rosenberg SE = 21). These metrics and his additional scales (SF-12 MCS, EQ-5D, and EQ-VAS) did not change appreciably and were within the normal range for the entire duration of 3.5-year follow-up at all different time points. Conclusion: With the increasing popularity of hand transplantation and the increasing awareness of the importance of psychosocial parameters in overall success, appropriate, comprehensive, and standardized measurements are important. These should be an integral part of patients’ screening and follow-up.

Background Many insects undergo a period of arrested development, called diapause, to avoid seasonally recurring adverse conditions. Whilst the phenology and endocrinology of insect diapause have been well studied, there has been comparatively little research into the developmental details of diapause. We investigated developmental aspects of diapause in sexually-produced embryos of the pea aphid, Acyrthosiphon pisum. Results We found that early stages of embryogenesis progressed at a temperature-independent rate, characteristic of diapause, whereas later stages of embryogenesis progressed at a temperature-dependent rate. However, embryos maintained at very high temperatures during the temperature-independent stage showed severe developmental abnormalities. Under no temperature regime did embryos display a distinct resting stage. Rather, morphological development progressed slowly but continuously throughout embryogenesis. Conclusion Diapause in the pea aphid, and perhaps in many other insects, is a temperature-independent slowing but not a cessation of morphological development. This suggests that the mechanisms limiting developmental rate during diapause may be the same as those controlling developmental rate at other stages of growth.