Faculty Bibliography

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

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.

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.

BACKGROUND: Venous outflow problems are the most common reasons for perioperative flap complications. Size mismatch in venous anastomoses poses a theoretical problem by promoting turbulent flow and subsequent thrombus formation. The purpose of this study was to determine if increased vein size mismatch is predictive of flap failure. METHODS: Retrospective review of our institutional flap registry from 1979 to 2016 identified 410 free flaps performed for reconstruction of lower extremity trauma. Patient demographics, flap characteristics, and flap outcomes were examined. Venous size mismatch was defined as a difference in size ≥ 1 mm between the recipient vein and flap vein. RESULTS: = 0.045; odds ratio: 2.58). CONCLUSION/CONCLUSIONS: Flaps with vein size mismatch ≥ 1 mm demonstrated increased flap complication rates in the setting of end-to-end venous anastomoses. End-to-side anastomosis was preferentially used in vein size mismatch and carried a higher risk of flap failure. Our results support using veins of similar size for anastomosis whenever feasible to protect against flap complications.

INTRODUCTION/BACKGROUND:The number of patients who may benefit from evaluation for face transplantation in the United States (US) remains largely unknown. The goal of our study was to better delineate the pool of patients who might benefit from face transplant evaluation based on the characteristics and mechanisms of injury of previously reported face transplant recipients. METHODS:The authors utilized data from the National Electronic Injury Surveillance System-All Injury Program in this study. The US Census Bureau data were used for population estimates. Inclusion and exclusion criteria were determined based on the characteristics of face transplant recipients to date, and the mechanisms of injury they sustained ultimately necessitating face transplantation. Statistical significance was reached if P <0.05. RESULTS:The estimated annual incidence of preventable craniofacial injuries from firearms (44,266-58,299; 31.7% increase), burns (5712-19,433; 240.2% increase), and animal attacks (5355-14,666; 173.9% increase) increased from 2005 to 2014, whereas the estimated annual incidence of craniofacial injuries from machinery (3927-2933; 25.3% decrease) decreased between 2005 and 2014. The authors estimate the annual incidence rate to fall between 32.1 per 100,000 and 58.1 per 100,000 among individuals aged 20 to 64 in the US. CONCLUSION/CONCLUSIONS:In this study, the authors estimate the annual incidence rate of individuals aged 20 to 64 in the US who may benefit from face transplant evaluation and believe that this quantification has the potential to initiate actionable discussions regarding geographical and financial factors affecting access to care in this patient population.