Faculty Bibliography

BACKGROUND:Acute rejection (AR) is a common complication in facial transplant (FT) patients associated with allograft edema and erythema. Our study aims to demonstrate the feasibility of using software-based 3-dimensional (3D) facial analysis to quantify edema as it resolves during/after AR treatment in an FT patient. METHODS:Our patient is a 23-year-old man who underwent a face and bilateral hand allotransplant in August 2020. The Vectra H1 (Canfield, Fairfield, NJ) portable scanner was used to capture 3D facial images at 8 time points between postoperative day (POD) 392 and 539. The images were analyzed with the Vectra Software using a rejection-free image (POD 539) as a control. RESULTS:Edema increased in the periorbital, lower third, and submandibular regions before AR treatment (POD 392-415). At POD 448, total facial edema was reduced to near baseline values in response to plasmapheresis and thymoglobulin (+156.94 to +28.2 mL). The fastest and most notable response to treatment was seen in the periorbital region, while some edema remained in the submandibular (+19.79 mL) and right lower third (+8.65 mL) regions. On POD 465, after the initial improvement, the edema increased but was resolved with steroid use. Facial edema did not correlate with the histopathological evaluation in our patient. CONCLUSIONS:We demonstrated the feasibility of analyzing 3D facial images to quantify edema during/after AR treatment in an FT patient. Our analysis detected edema changes consistent with AR followed by an improvement after treatment. This technology shows promise for noninvasive monitoring of FT patients.

Although the ethical and technical feasibility of face transplant (FT) has been established, current literature lacks consensus on functional outcomes monitoring for recipients. This systematic review aims to appraise and summarize the current literature on tools used to assess motor functional outcomes in FT. This study complied with the guidelines outlined in the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA). On September 15, 2020, two reviewers conducted independent electronic searches using medical literature databases, without language or time frame limitations. Eligibility criteria included studies reporting on the evaluation of motor functional outcomes in face transplant recipients. Of 451 papers found in the literature, 12 fulfilled the study inclusion criteria. The reported tools included clinical scales/examinations, electromyography, optical movement tracking devices, muscle volumetric measurement using magnetic resonance imaging, and software-based video and photo analyses. The frequency of data collection varied from every three months to every year. Publications reporting on motor functional outcomes tracking tools vary broadly and demonstrate a lack of consensus. Although quantitative measurements are desirable, adapted clinical scales are still the current standard of care.

BACKGROUND:Vascularized composite allotransplantation (VCA) has redefined the frontiers of plastic and reconstructive surgery. At the cutting edge of this evolving paradigm, we present the first successful combined full face and bilateral hand transplant (FT-BHT). METHODS:A 21-year-old man with sequelae of an 80% total body surface area burn injury sustained following a motor vehicle accident presented for evaluation. The injury included full face and bilateral upper extremity composite tissue defects, resulting in reduced quality of life and loss of independence. Multidisciplinary evaluation confirmed eligibility for combined FT-BHT. The operative approach was validated through 11 cadaveric rehearsals utilizing computerized surgical planning. Institutional review board and organ procurement organization approvals were obtained. The recipient, his caregiver, and the donor family consented to the procedure. RESULTS:Combined full face (eyelids, ears, nose, lips, and skeletal subunits) and bilateral hand transplantation (forearm level) was performed over 23 hours on August 12-13th, 2020. Triple induction and maintenance immunosuppressive therapy and infection prophylaxis were administered. Plasmapheresis was necessary postoperatively. Minor revisions were performed over seven subsequent operations, including five left upper extremity, seven right upper extremity, and seven facial secondary procedures. At eight months, the patient is approaching functional independence and remains free of acute rejection. He has significantly improved range of motion, motor power, and sensation of the face and hand allografts. CONCLUSION/CONCLUSIONS:Combined FT-BHT is feasible. This is the most comprehensive VCA procedure successfully performed to date, marking a new milestone in plastic and reconstructive surgery for patients with otherwise irremediable injuries.

LEARNING OBJECTIVES/OBJECTIVE:After studying this article, the participant should be able to: 1. Appreciate the evolution and increasing complexity of transplanted facial allografts over the past two decades. 2. Discuss indications and contraindications for facial transplantation, and donor and recipient selection criteria and considerations. 3. Discuss logistical, immunologic, and cost considerations in facial transplantation, in addition to emerging technologies used. 4. Understand surgical approaches and anatomical and technical nuances of the procedure. 5. Describe aesthetic, functional, and psychosocial outcomes of facial transplantation reported to date. SUMMARY/CONCLUSIONS:This CME article highlights principles and evolving concepts in facial transplantation. The field has witnessed significant advances over the past two decades, with more than 40 face transplants reported to date. The procedure now occupies the highest rung on the reconstructive ladder for patients with extensive facial disfigurement who are not amenable to autologous reconstructive approaches, in pursuit of optimal functional and aesthetic outcomes. Indications, contraindications, and donor and recipient considerations for the procedure are discussed. The authors also review logistical, immunologic, and cost considerations of facial transplantation. Surgical approaches to allograft procurement and transplantation, in addition to technical and anatomical nuances of the procedure, are provided. Finally, the authors review aesthetic, functional, and psychosocial outcomes that have been reported to date.

Understanding the risk factors that contribute to post-mastectomy complications can better inform preoperative discussions. Here, we assess the impact of the 5-Factor Frailty Index Score (mFI-5) in predicting 30-day postoperative complications in patients undergoing mastectomy. A retrospective review of the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) data base was conducted for patients older than 65 undergoing mastectomy between 2010 and 2015. We assessed each patient's Frailty Index Score using the mFI-5. Primary outcomes included wound complications and overall complications. Multivariate logistic and linear regression analyses were used to determine the ability of the mFI-5 to predict postoperative outcomes. A total of 13,783 patients were analyzed. The rate of wound complications was 3.0%, while the rate of overall complications was 6.0%. An mFI-5 score greater than 2 was an independent risk factor for wound complications and overall complications. Overall, patients undergoing mastectomy with an mFI-5 of 2 or greater experienced higher rates of postoperative complications. The mFI-5 is an accessible tool that can be used to risk-stratify patients undergoing mastectomy and can positively contribute to the informed consent and shared decision-making process.

Purpose: Skin biopsies are currently the gold standard for evaluating the inflammatory status of face allografts. However, "tape stripping" is emerging as a noninvasive technique to monitor autoimmune/auto inflammatory skin diseases. This technique, highly suitable for serial sampling and combined with high sensitive PCR assays, could revolutionize molecular monitoring the face allograft status. Herein, we tested the hypothesis that isolation of total RNA and gene expression profiling are feasible using skin samples collected using tape strips.
Method(s): Tape strips (CuDerm Corporation, Texas) were used to obtain RNA from two face transplant recipients. Each tape strip is comprised of 10 discs. Allograft skin area was marked, cleaned with alcohol, and 8 samples (8 tape strips) were obtained. Each disc (10 discs from one sample) was immersed in 1ml RLT buffer with 100ul beta-mercaptoethanol. RNA was isolated from the tape strip skin samples using the RNeasy mini kit. We quantified total RNA using A260/A280 ratio, reverse transcribed RNA into cDNA and pre-amplified cDNA using oligonucleotide primer pairs for a custom panel of mRNAs. We measured absolute levels of mRNA for Keratin 15, MIP1alpha, and MIP1beta, as well as 18S rRNA by preamplification enhanced real time quantitative PCR assays (RT-qPCR assays) using Quant Studio 6. We designed gene specific Taqman primers and probes to amplify and detect gene of interest and a customized BAK amplicon to develop a standard curve for absolute quantification of transcript copies per microgram of total RNA.
Result(s): Median quantity of total RNA from the tape strips was 64.48ng. Individual and the median number of total RNA, individual and the median number of the reference gene 18S rRNA, and individual and median number of mRNA copies of Keratin 15, MIP1alpha, and MIP1beta are shown in Figure 1.
Conclusion(s): We have demonstrated the feasibility of isolating total RNA from tape strips and quantifying transcript abundance. Further refinement of this technology is ongoing in our laboratory. Tape strip based molecular monitoring of face transplant recipients may offer a noninvasive substitute for allograft biopsies

BACKGROUND:The operating microscope is used in many centers for microvascular hepatic arterial reconstruction in living as well as deceased donor liver transplantation in adult and pediatric recipients. To date, a systematic review of the literature examining this topic is lacking. METHODS:This systematic review of the literature was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Three different electronic databases (PubMed, Embase OVID, and Cochrane CENTRAL) were queried. RESULTS:A total of 34 studies were included. The rate of hepatic artery thrombosis (HAT) in noncomparative studies (28) ranged from 0% to 10%, with 8 studies reporting patient deaths resulting from HAT. Within comparative studies, the rate of HAT in patients who underwent arterial reconstruction using the operating microscope ranged from 0% to 5.3%, whereas the rate of HAT in patients who underwent arterial reconstruction using loupe magnification ranged from 0% up to 28.6%, and 2 studies reported patient deaths resulting from HAT. Two comparative studies did not find statistically significant differences between the 2 groups. CONCLUSIONS:Our comprehensive systematic review of the literature seems to suggest that overall, rates of HAT may be lower when the operating microscope is used for hepatic arterial reconstruction in liver transplantation. However, matched comparisons are lacking and surgical teams need to be mindful of the learning curve associated with the use of the operating microscope as compared with loupe magnification, as well as the logistical and time constraints associated with setup of the operating microscope.

Unveiling the molecular mechanisms underlying tissue regeneration provides new opportunities to develop treatments for diabetic ulcers and other chronic skin lesions. Here, we show that Ccl2 secretion by epidermal keratinocytes is directly orchestrated by Nrf2, a prominent transcriptional regulator of tissue regeneration that is activated early after cutaneous injury. Through a unique feedback mechanism, we find that Ccl2 from epidermal keratinocytes not only drives chemotaxis of macrophages into the wound but also triggers macrophage expression of EGF, which in turn activates basal epidermal keratinocyte proliferation. Notably, we find dysfunctional activation of Nrf2 in epidermal keratinocytes of diabetic mice after wounding, which partly explains regenerative impairments associated with diabetes. These findings provide mechanistic insight into the critical relationship between keratinocyte and macrophage signaling during tissue repair, providing the basis for continued investigation of the therapeutic value of Nrf2.

Chronic venous insufficiency (CVI) stems from venous hypertension, extravasation of blood, and iron-rich skin deposits. The latter is central to ulcer development through generating reactive oxygen species (ROS) that drive persistent local inflammation and the development of lipodermatosclerosis. The ability to study CVI cutaneous inflammation is fundamental to advancing therapies. To address this end, a novel protocol was adapted to investigate cutaneous wound healing in iron-induced inflammation.