Faculty Bibliography

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.

We longitudinally assessed speech intelligibility (percent words correct/pwc), communication efficiency (intelligible words per minute/iwpm), temporal control markers (speech and pause coefficients of variation), and formant frequencies associated with lip motion in a 41-year-old face transplant recipient. Pwc and iwpm at 13 months post-transplantation were both higher than preoperative values. Multivariate regression demonstrated that temporal markers and all formant frequencies associated with lip motion were significant predictors (P < 0.05) of communication efficiency, highlighting the interplay of these variables in generating intelligible and effective speech. These findings can guide us in developing personalized rehabilitative approaches in face transplant recipients for optimal speech outcomes.

Background/UNASSIGNED:A major challenge in face transplantation (FT) is the limited donor allograft pool. This study aimed to investigate the feasibility of cross-sex FT (CSFT) for donor pool expansion by: (1) comparing craniomaxillofacial metrics following CSFT versus same-sex FT (SSFT); and (2) evaluating the public and medical professionals' perception of CSFT. Methods/UNASSIGNED:Seven cadaveric FTs were performed, resulting in both CSFT and SSFT. Precision of bony and soft tissue inset was evaluated by comparing pre- versus post-operative cephalometric and anthropometric measurements. Fidelity of the FT compared to the virtual plan was assessed by imaging overlay techniques. Surveys were administered to medical professionals, medical students, and general population to evaluate opinions regarding CSFT. Results/UNASSIGNED:< 0.001). On non-blinded and blinded assessments, 62.9% and 79% of responses rated the CSFT superior or equal to SSFT, respectively. Conclusions/UNASSIGNED:Our study demonstrates similar anthropometric and cephalometric outcomes for CSFT and SSFT. Participants were more reticent to undergo CSFT, with increased willingness if supported by research. CSFT may represent a viable option for expansion of the donor pool in future patients prepared to undergo transplantation.

Due to the high complication rate of panniculectomies, preoperative risk stratification is imperative. This study aimed to assess the predictive value of the 5-item modified frailty index (mFI-5) for postoperative complications in the elderly following panniculectomy.