A World Update of Progress in Lower Extremity Transplantation: What's Hot and What's Not.

ABSTRACT: The field of vascularized composite allotransplantation (VCA) is the new frontier of solid organ transplantation (SOT). VCA spans life-enhancing/life-changing procedures such as upper extremity, craniofacial (including eye), laryngeal, tracheal, abdominal wall, penis, and lower extremity transplants. VCAs such as uterus transplants are life giving unlike any other SOT. Of all VCAs that have shown successful intermediate- to long-term graft survival with functional and immunologic outcomes, lower extremity VCAs have remained largely underexplored. Lower extremity transplantation (LET) can offer patients with improved function compared to the use of conventional prostheses, reducing concerns of phantom limb pain and stump complications, and offer an option for eligible amputees that either fail prosthetic rehabilitation or do not adapt to prosthetics. Nevertheless, these benefits must be carefully weighed against the risks of VCA, which are not trivial, including the adverse effects of lifelong immunosuppression, extremely challenging perioperative care, and delayed nerve regeneration. There have been 5 lower extremity transplants to date, ranging from unilateral or bilateral to quadrimembral, progressively increasing in risk that resulted in fatalities in 3 of the 5 cases, emphasizing the inherent risks. The advantages of LET over prosthetics must be carefully weighed, demanding rigorous candidate selection for optimal outcomes.

Functional Reconstruction of Arches of the Foot With Vascularized Fibula Flap.

ABSTRACT: The skeletal integrity of the foot is as important as the soft tissue coverage of the foot. In this article, we present reconstruction of arches of foot with free fibula flap. Three patients with composite foot defects underwent reconstruction a with vascularized fibula flap. Free fibula flap was used to reconstruct the transverse arch in 2 cases and longitudinal arch in 1 case. The mean follow-up period was 3.2 years. Functional outcome was evaluated with 3-dimensional motion analyses at 12 months postoperatively. No early or late complications were encountered, and all patients were satisfied with both cosmetic appearance and functional aspects of their foot. Fibular bone showed a very healthy course without any fracture, resorption, extrusion, or migration. Three-dimensional motion analyses revealed acceptable gait capability in all cases showing successful restoration of the foot arches. As a conclusion, osteocutaneous free fibula flap can provide functional and durable reconstruction of longitudinal and transverse arches of the foot, especially if preservation of the length or the width of the foot is desired.

Composite tissue xenopreservation: Preliminary results of staged VCA in rat to mouse model.

BACKGROUND: The time between procurement and transplantation of composite tissues, especially regarding the limited donor pool, is a challenge effecting the outcomes of the transplantation. Current preservation techniques mainly include either cold preservation with a solution or machine perfusion using blood or certain oxygen-carrying solutions. However, none enables preservation beyond 24 h. Increasing this time to several days will provide better usage of the donor pool, safer transplantation of VCA with significant muscle content, and gives time to stabilize a patient before long surgical procedures. Herein, we described a novel strategy of xenopreservation (preservation via xenotransplantation) to preserve composite tissues for 7 days, followed by staged transplantation. MATERIALS AND METHODS: We used two concordant species, female Sprague Dawley rats (n = 10) and female CF-1 mice (n = 10) in this study. Four of pair of animals are used for anatomical study. The groin flap of the rat was used as a xenograft and xenotransplanted to the neck area of the carrier mouse. Cyclosporine (CsA) was administered used as immunosuppressant. After 7 days of preservation on the mouse neck, xenotransplanted groin flap (called xenopreserved flap) was re-harvested, skin and vessels samples were collected for histopathological evaluation, and the xenopreserved flap was transplanted to the donor rat's opposite groin area. Anastomoses were performed between the flap's pedicle and the femoral vessels. Clinical observation regarding inflammation and tissue perfusion of the xenopreserved flap was monitored daily. Fifteen days after the second surgical procedure, the rats were euthanized, and skin and vessel samples were collected. Histologic evaluation, including inflammatory cell numbers, was performed. Wilcoxon test was used to compare the changes in inflammation severity and p < .05 was set for statistical significance. RESULTS: All xenopreserved groin flaps except one survived. Mean lymphocyte count before the second operation (at the end of the xenopreservation procedure) was 20,22 ± 0.44 and reduced to 13,14 ± 0.47 at the end of 15 days, and the difference was statistically significant (p < .05). CONCLUSION: This proof-of-concept study with preliminary results showed that xenotransplantation might be a novel strategy for preservation of VCA for a certain period of time. However, additional translational studies are needed to modulate the tissue changes following xenopreservation.

Novel cell-based strategies for immunomodulation in vascularized composite allotransplantation.

PURPOSE OF REVIEW: Vascularized composite allotransplantation (VCA) has become a clinical reality in the past two decades. However, its routine clinical applications are limited by the risk of acute rejection, and the side effects of the lifelong immunosuppression. Therefore, there is a need for new protocols to induce tolerance and extend VCA survival. Cell- based therapies have emerged as an attractive strategy for tolerance induction in VCA. This manuscript reviews the current strategies and applications of cell-based therapies for tolerance induction in VCA. RECENT FINDINGS: Cellular therapies, including the application of bone marrow cells (BMC), mesenchymal stem cells (MSC), adipose stem cells, regulatory T cells (Treg) cells, dendritic cells and donor recipient chimeric cells (DRCC) show promising potential as a strategy to induce tolerance in VCA. Ongoing basic science research aims to provide insights into the mechanisms of action, homing, functional specialization and standardization of these cellular therapies. Additionally, translational preclinical and clinical studies are underway, showing encouraging outcomes. SUMMARY: Cellular therapies hold great potential and are supported by preclinical studies and clinical trials demonstrating safety and efficacy. However, further research is needed to develop novel cell-based immunosuppressive protocol for VCA.

Treg-inducing microparticles promote donor-specific tolerance in experimental vascularized composite allotransplantation.

For individuals who sustain devastating composite tissue loss, vascularized composite allotransplantation (VCA; e.g., hand and face transplantation) has the potential to restore appearance and function of the damaged tissues. As with solid organ transplantation, however, rejection must be controlled by multidrug systemic immunosuppression with substantial side effects. As an alternative therapeutic approach inspired by natural mechanisms the body uses to control inflammation, we developed a system to enrich regulatory T cells (Tregs) in an allograft. Microparticles were engineered to sustainably release TGF-ß1, IL-2, and rapamycin, to induce Treg differentiation from naïve T cells. In a rat hindlimb VCA model, local administration of this Treg-inducing system, referred to as TRI-MP, prolonged allograft survival indefinitely without long-term systemic immunosuppression. TRI-MP treatment reduced expression of inflammatory mediators and enhanced expression of Treg-associated cytokines in allograft tissue. TRI-MP also enriched Treg and reduced inflammatory Th1 populations in allograft draining lymph nodes. This local immunotherapy imparted systemic donor-specific tolerance in otherwise immunocompetent rats, as evidenced by acceptance of secondary skin grafts from the hindlimb donor strain and rejection of skin grafts from a third-party donor strain. Ultimately, this therapeutic approach may reduce, or even eliminate, the need for systemic immunosuppression in VCA or solid organ transplantation.

The effect of thymus transplantation on donor-specific chimerism in the rat model of composite osseomusculocutaneous sternum, ribs, thymus, pectoralis muscles, and skin allotransplantation.

INTRODUCTION: Research on tolerance has proven that development of donor-specific chimerism (DSC) may accompany tolerance induction in vascularized composite allotransplantation (VCA). In this study, we aimed to determine the effect of thymus transplantation on the induction of DSC in rat VCA model of osseomusculocutaneous sternum (OMCS) and osseomusculocutaneous sternum and thymus (OMCST) allotransplantation. MATERIALS AND METHODS: A total of 20 Lewis-Brown Norway and Lewis rats, 5-6 weeks old, weighting between 120 and 150 g, were used in the study. OMCS (n = 5) and OMCST (n = 5) allografts were harvested from Lewis-Brown Norway donors (RT1l + n ) based on the common carotid artery and external jugular vein, and a heterotopic transplantation was performed to the inguinal region of the Lewis (RT1l ) recipients under cyclosporine A monotherapy (16 mg/kg) protocol tapered to 2 mg/kg and maintained for the duration of the study. The peripheral blood chimerism levels (T-cell, B-cell, and monocyte/granulocyte/dendritic cell-MGDC populations) were evaluated at days 7, 14, 35, 63, 100, and 150 posttransplant by flow cytometry. At Day 150, thymus, spleen, and liver samples were assessed by polymerase chain reaction (PCR) in the presence of DSC. RESULTS: Total chimerism level increased in both OMCST and OMCS groups at all time points. At 150 days posttransplant, chimerism in OMCST group was significantly higher (12.91 ± 0.16%) than that in OMCS group (8.89 ± 0.53%%, p < .01), and PCR confirmed the presence of donor-derived cells in the liver and spleen of all OMCST recipients and in one liver sample and two spleen samples in OMCS recipients without thymus transplant. CONCLUSIONS: This study confirmed the direct effects of thymus transplantation on the induction and maintenance of DSC in T-cell, B-cell, and MGDC populations. These results confirm correlation between thymus transplantation and DSC induction.

Immunological considerations and concerns as pertinent to whole eye transplantation.

PURPOSE OF REVIEW: The advent of clinical vascularized composite allotransplantation (VCA), offers hope for whole eye transplantation (WET) in patients with devastating vison loss that fails or defies current treatment options. Optic nerve regeneration and reintegration remain the overarching hurdles to WET. However, the realization of WET may indeed be limited by our lack of understanding of the singular immunological features of the eye as pertinent to graft survival and functional vision restoration in the setting of transplantation. RECENT FINDINGS: Like other VCA, such as the hand or face, the eye includes multiple tissues with distinct embryonic lineage and differential antigenicity. The ultimate goal of vision restoration through WET requires optimal immune modulation of the graft for successful optic nerve regeneration. Our team is exploring barriers to our understanding of the immunology of the eye in the context of WET including the role of immune privilege and lymphatic drainage on rejection, as well as the effects ischemia, reperfusion injury and rejection on optic nerve regeneration. SUMMARY: Elucidation of the unique immunological responses in the eye and adnexa after WET will provide foundational clues that will help inform therapies that prevent immune rejection without hindering optic nerve regeneration or reintegration.

Case Report: Late Reconstruction of the Land Mine-Injured Heel With an Osteomyocutaneous Composite Fibular Flap.

The heel comprises the epidermis, minimal subcutaneous tissue, a dense septum, and the calcaneus. Injury to any of these structures can impair the ability to walk. The soft tissue or calcaneal bone can be injured by trauma. Injuries incurred in war are usually high-energy traumas caused by weapons such as rifles, rockets, and land mines. Such injuries can be life threatening and involve the loss of tissue, including skin, soft tissue, bone, and neurovascular tissue. Two main treatment protocols are used for such injuries with large tissue defects: amputation and reconstruction. We describe a reconstruction with an osteomyocutaneous fibular flap for a heel injury. At the 2-year follow-up point, the patient had 30% loss of ankle range of motion. The visual analog scale score had dramatically decreased from 8 to 1, and the patient was satisfied with the result. In conclusion, patients with significant problems such as infection, pain, and anatomic deterioration of the calcaneus can be successfully treated using an osteomyocutaneous fibular flap in a single surgery.

A new total hemiface allotransplantation model in rats.

INTRODUCTION: Vascularized composite allotransplantation (VCA), a new reconstructive option for patients suffering from extensive facial defects leads to superior functional and aesthetic outcomes compared to the standard autologous reconstruction. Among VCA recipients, each case involves different facial structures and tissues depending on the patient's injury, thus drawing conclusions on the mechanism of immune interactions between the donor and recipient is challenging. This study introduces a new total hemiface VCA model, including scalp, external ear, mystacial pad, premaxilla, upper/lower lids, nose, and upper/lower lips to evaluate the effect of transplantation of multitissue VCA on the recipient's immune response. MATERIAL AND METHODS: Ten hemiface allotransplantations were performed in two groups between Lewis-Lewis (isograft) and LBN-Lewis (allograft) rats. Cyclosporine A (CsA) monotherapy was applied in the allograft group to prevent rejection. RESULTS: All flaps survived up to 100 days post-transplant. The mean warm ischemia time was 45 minutes. Histological analysis revealed normal bone, cartilage (ear and nose), conjunctiva, palpebra, and eyelashes. Flow cytometry confirmed donor-specific chimerism for T cells (CD4/RT1(n) and CD8/RT1(n)) and B cells (CD45RA/RT1(n)) in the peripheral blood of all rats in the allotransplantation group. At post-transplant day 7, chimerism levels were at 1.68% for CD4/RT1(n) , 0.46% for CD8/RT1(n) and 0.64% for CD45RA/RT1(n). However, chimerism levels for CD4/RT1(n), CD8/RT1(n), and CD45RA/RT1(n) populations decreased at long-term follow-up (at post-transplant day 100) to 0.08%, 0.04%, and 0.23%, respectively. CONCLUSION: The feasibility and long-term survival of the new hemiface VCA transplantation model was confirmed, donor-specific chimerism and post-transplant tissue changes were evaluated.

Challenging Breast Augmentations: The Influence of Preoperative Anatomical Features on the Final Result.

BACKGROUND: Achieving satisfactory results may be difficult in augmentation mammaplasty patients in the presence of breast, chest wall, or vertebral deformities. These deformities have not been classified previously, and the impact of each deformity or combination of deformities has not been defined. OBJECTIVES: The aims of this study are to determine the complicating factors in augmentation mammaplasty, to classify these factors according to their influence on surgical outcome, and to develop an identification system for simplifying the recognition of challenging cases. METHODS: We retrospectively analyzed photographs and records of 100 consecutive patients who underwent augmentation mammaplasty. We observed suboptimal results in 18 cases. Preoperative deformities of the breast, chest wall, and vertebra were recorded in order to determine which factor or factors had complicated the surgeries. Eventually, the relationship between suboptimal surgical results and complicating factors was evaluated. RESULTS: We observed that some deformities alone caused suboptimal results, whereas others did not. Deformities that caused suboptimal results alone were called major complicating factors, and any others were called minor complicating factors. We observed that suboptimal results were also obtained in patients who had four minor complicating factors. Patients who had suboptimal results because of major or minor complicating factors were considered challenging cases. CONCLUSIONS: In this study, complicating factors for augmentation mammaplasty were defined and classified as major or minor depending on their effect on the surgical outcome. We suggest an identification system that simplifies the recognition of challenging cases in breast augmentation.

Minced nerve tissue in vein grafts used as conduits in rat tibial nerves.

INTRODUCTION: Peripheral nerve injuries are encountered frequently in clinical practice. In nerve repair, an end-to-end suture is the preferable choice of treatment. However, where primary closure is not possible, the defect is to be repaired with a nerve graft. METHODS: A total of 21 female Wistar rats weighing 230 to 290 g were used in the study. They were classified into the following 3 groups: (I) nerve graft, (II) vein graft, and (III) minced nerve graft. In group I, after exposure of the tibial nerve, a 1-cm-long nerve gap was created on the tibial nerve, and the defect was repaired epineurally by using the autogenous nerve. In group II, the 1-cm tibial nerve defect was repaired by using an autogenous vein graft. In group III, a 1-cm nerve graft was divided to 3 equal parts, with one of the nerve parts being minced with microscissors and placed in the vein graft lumen. Thereafter, a 1-cm tibial nerve defect was repaired by the vein graft filled with minced nerve tissue. The tibial function indices (TFIs) were calculated for functional assessment using the Bain-Mackinnon-Hunter formula. Light and electron microscopic evaluations were performed for morphometric assessment. In addition, the myelinated fibers were counted in all groups. RESULTS: The TFIs of group II were found to be the lowest among all the groups after the sixth week, whereas the TFI of group I was found to be better than the other groups after the sixth week. There was no difference in TFIs between group I and group III. On the basis of the number of myelinated fibers, there was no statistically significant difference between group I and group III, whereas the difference was significant (P<0.05) between groups I/III and group II. Presence of peripheral nerves in light microscopic evaluation revealed normal characteristics of myelinated fibers in all groups. The myelinated axon profile was near normal in the nerve graft group in electron microscopic evaluation. However, there were more degenerated axons with disturbed contours and vacuolizations in the vein graft group compared to the minced nerve graft group. CONCLUSIONS: We can conclude that using minced nerve tissue in vein grafts as a conduit increases the regeneration of nerves (almost like the nerve graft group) and it may not be caused by donor-site morbidity. It can be used in the repair of nerve defects instead of autogenous nerve grafts after further experimental evidence and clinical trials.

Custom-made approach to a patient with post-burn breast deformity.

Second and third degree burns on breasts at preadolescent period may cause severe breast deformations. This deformation can be variable depending on severity and location of the burns, personal adolescent patterns, and treatment modality in acute burn period. A 21 year old female patient admitted to our department for her breast deformation due to burn contracture at the inferior pole of the right breast. On physical examination we defined that development of the volume of the right breast was equal to the left, and inferior pole of the right breast was flattened due to contracture, and nipple was projected to inferior. We found that inframammary crease of the right breast was 2 cm lower than that of left; andthe distance of nipple-inframamary crease was 4.7 cm while areola-inframmary crease was 2 cm. New nipple-areola complex level was identified according to left breast's level. Medial and lateral lines were planned to merge inferiorly at 2 cm above inframmary crease in a plan similar to vertical mammaplasty. Superior pedicle carrying nipple areola was desepitelised. Lower parenchymal V flap was transposed superiorly and attached to the pectoral muscle. Inferior parts of the lateral and medial glandular flaps were excised to form new inframammary crease. The desired laxity of skin at the lower pole was obtained by performing a new Z- plasty between lateral and medial skin flaps. Breast symmetry was confirmed by postoperative objective measurements between left and right breasts. Patient's satisfaction and aesthetic appearance levels were high. Breasts deformation patterns caused by burns, trauma and mass exsicion due to cancer could not be addressed with traditional defined techniques. Special deformations can be corrected by custom made plannings as we presented here.

Definitive foot drop deformity repair with tensor fascia latae myocutaneous flap.

Tensor fascia latae (TFL) myocutaneous flap, utilized as a novel approach for the successful functional repair of the foot drop deformity is presented in this case report. A 21-year-old male patient was subjected to a close-range high-velocity gunshot injury and sustained comminuted Gustillo-type IIIB open fracture of his left tibia. A composite skin and soft tissue defect including tibialis anterior and extansor hallucis longus tendons was determined. The injury was managed in two stages. In the first stage, the immediate reconstruction of the open tibia fracture was provided by using a reverse flow sural flap and external fixation of the fracture. The functional restoration was achieved by vascular fascia latae in the second stage, 6 months after the initial skin, soft tissue, and bone defect repair. The functional recovery was successful, and the foot drop gait was almost totally ameliorated. Reconstruction with TFL flap should be retained in the armamentarium for the functional repair of the foot drop deformity, caused by composite skin and soft tissue defects of the pretibial region.

One-and-a-half-barrel vascularized free fibular flap for the reconstruction of segmental mandibular defect.

We designed one-and-a-half-barrel vascularized free fibular flap which is a further modification of the double-barrel technique, and we tried to overcome the discrepancy between mandible and fibula flap. We used this flap in case of a segmental mandibular defect that occurred as a result of a giant cell reparative granuloma excision. This new modification eliminated volume insufficiency of the classical technique and volume excess of the double-barrel technique.A segmental mandibular defect that occurred as a result of giant cell reparative granuloma excision was reconstructed using one-and-a-half-barrel vascularized free fibular flap. The size discrepancy between mandible and free fibula flap is a well-known problem, and this new modification of free fibular flap eliminated volume insufficiency or excess problems of the other techniques.

Reconstruction of the great toe tip defect with a pedicled heterodigital artery flap.

UNLABELLED: Reconstruction of the foot's distal portion has always been a difficult problem in plastic surgery. Moreover, isolated soft tissue defects of the hallux are not common in daily practice. In the case of tissue loss over the hallux, it is common practice to treat the soft tissue defect conservatively or to apply a skin graft. But the loss of tissue leaves a shortened, hypersensitive, and deformed toe. A method for reconstruction of a soft tissue defect on the tip of the hallux by means of a pedicled heterodigital artery flap from the second toe is presented, and alternative flap choices for this challenging area of the distal foot are discussed. To the best of the authors' knowledge, this surgical approach for reconstruction of hallux tip defects has not been reported previously. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Osteocutaneous Fibular Flap for Reconstruction of Composite Metacarpal Defects Due to Gunshot Wounds.

Background: Gunshot wounds of the hand are challenging, as these injuries include bones, tendons neurovascular structures, and soft tissue. The osteocutaneous fibula flap has shown to be an excellent option for treating the composite defects, including bone and soft tissue. In this study, reconstructions of gunshot injuries of the metacarpal bones with a fibular flap are presented. Methods: Six patients with gunshot injuries to the hand were treated with free fibula flap. All patients had composite defects reconstructed with osteocutaneous fibula flap. Because of the size mismatch between fibula and metacarpal bone, a longitudinally split fibula was used in 2 patients. In 1 patient, the flap was used in a double-barrel fashion to reconstruct 2 metacarpal bone losses. Tendon repairs were performed either primarily or with tendon graft. All patients received hand rehabilitation. Hand function of the patients was evaluated by grip and pinch strength tests and Jebsen hand function test. Results: All flaps survived with no major postoperative complications. The mean follow-up period was 18 months. Web releasing and an arthrodesis procedure was performed in 1 patient, and tenolysis was performed in 2 others. All flaps adapted well to the recipient area. With respect to routine daily activities, overall hand function measured by grip and pinch strength tests and Jebsen hand function test was considered satisfactory in all patients. Conclusions: The fibular flap is a good alternative for reconstruction of the injured hand with composite defects, including metacarpal bone and soft tissue. It can be used longitudinally or transversely. Osteotomies can be performed to obtain split fibular flap or double-barrel fibular flap according to the bone defect.

A Reversibly Thermoresponsive, Theranostic Nanoemulgel for Tacrolimus Delivery to Activated Macrophages: Formulation and In Vitro Validation.

Despite long-term immunosuppression, organ transplant recipients face the risk of immune rejection and graft loss. Tacrolimus (TAC, FK506, Prograf®) is an FDA-approved keystone immunosuppressant for preventing transplant rejection. However, it undergoes extensive first-pass metabolism and has a narrow therapeutic window, which leads to erratic bioavailability and toxicity. Local delivery of TAC directly into the graft, instead of systemic delivery, can improve safety, efficacy, and tolerability. Macrophages have emerged as promising therapeutic targets as their increased levels correlate with an increased risk of organ rejection and a poor prognosis post-transplantation. Here, we present a locally injectable drug delivery platform for macrophages, where TAC is incorporated into a colloidally stable nanoemulsion and then formulated as a reversibly thermoresponsive, pluronic-based nanoemulgel (NEG). This novel formulation is designed to undergo a sol-to-gel transition at physiological temperature to sustain TAC release in situ at the site of local application. We also show that TAC-NEG mitigates the release of proinflammatory cytokines and nitric oxide from lipopolysaccharide (LPS)-activated macrophages. To the best of our knowledge, this is the first TAC-loaded nanoemulgel with demonstrated anti-inflammatory effects on macrophages in vitro.

Peripheral nerve repair is associated with augmented cross-tissue inflammation following vascularized composite allotransplantation.

Introduction: Vascularized composite allotransplantation (VCA), with nerve repair/coaptation (NR) and tacrolimus (TAC) immunosuppressive therapy, is used to repair devastating traumatic injuries but is often complicated by inflammation spanning multiple tissues. We identified the parallel upregulation of transcriptional pathways involving chemokine signaling, T-cell receptor signaling, Th17, Th1, and Th2 pathways in skin and nerve tissue in complete VCA rejection compared to baseline in 7 human hand transplants and defined increasing complexity of protein-level dynamic networks involving chemokine, Th1, and Th17 pathways as a function of rejection severity in 5 of these patients. We next hypothesized that neural mechanisms may regulate the complex spatiotemporal evolution of rejection-associated inflammation post-VCA. Methods: For mechanistic and ethical reasons, protein-level inflammatory mediators in tissues from Lewis rats (8 per group) receiving either syngeneic (Lewis) or allogeneic (Brown-Norway) orthotopic hind limb transplants in combination with TAC, with and without sciatic NR, were compared to human hand transplant samples using computational methods. Results: In cross-correlation analyses of these mediators, VCA tissues from human hand transplants (which included NR) were most similar to those from rats undergoing VCA + NR. Based on dynamic hypergraph analyses, NR following either syngeneic or allogeneic transplantation in rats was associated with greater trans-compartmental localization of early inflammatory mediators vs. no-NR, and impaired downregulation of mediators including IL-17A at later times. Discussion: Thus, NR, while considered necessary for restoring graft function, may also result in dysregulated and mis-compartmentalized inflammation post-VCA and therefore necessitate mitigation strategies. Our novel computational pipeline may also yield translational, spatiotemporal insights in other contexts.

Two-stage surgical approach with dermofat graft and lipofilling for the treatment of established Frey syndrome and facial depression deformity.

Frey syndrome and facial contour deformity commonly occur after parotid surgery. Although the treatment of established Frey syndrome has focused on medical solutions, surgical solutions to established Frey syndrome have been less reported. Moreover, these methods may not resolve the facial depression. In the presented case here, we used 2-stage surgical approach with dermofat graft and lipofilling for the treatment of established Frey syndrome and facial depression deformity. We considered that this technique provides the easiest, most practical, satisfying, and effective solution for Frey syndrome that develops in the late follow-up period after superficial parotidectomy.

Experience with vertical mammaplasty: advantages and drawbacks of Hall-Findlay's superomedial pedicle technique and improving the results by adding modifications to the technique.

BACKGROUND: Vertical techniques have become a growing area in reduction mammaplasty. Although it has many advantages such as a smaller scar and durable results, some problems still persist. The Hall-Findlay superomedial pedicle technique is one approach to obtain better results but is not without drawbacks. Some modifications are suggested to overcome its problems. METHODS: Superior pedicle vertical mammaplasty was performed for mastopexy, and superior, superomedial, and modified superomedial techniques were used for the reduction cases. Patients were followed up for at least 2 years and the complications were determined. RESULTS: Mastopexy cases had almost no complications. In reduction cases, the most common problems involved circulation and scar widening with the superior pedicle technique and bottoming-out deformity with the superomedial Hall-Findlay technique. These were negligible in its modified form. CONCLUSIONS: The tightness in the infra-areolar site is very important for a durable breast shape. Although the Hall-Findlay superomedial pedicle technique offers a versatile composite block nipple-areola complex with its sensation maintained, the inferior part of the pedicle that makes the medial pillar is in excess and the same amount of tissue must be removed from the lateral pillar to ensure tightness. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .