Emile N. Brown

Rtp801, a suppressor of mTOR signaling, is an essential mediator of cigarette smoke-induced pulmonary injury and emphysema

Rtp801 (also known as Redd1, and encoded by Ddit4), a stress-related protein triggered by adverse environmental conditions, inhibits mammalian target of rapamycin (mTOR) by stabilizing the TSC1-TSC2 inhibitory complex and enhances oxidative stress–dependent cell death. We postulated that Rtp801 acts as a potential amplifying switch in the development of cigarette smoke–induced lung injury, leading to emphysema. Rtp801 mRNA and protein were overexpressed in human emphysematous lungs and in lungs of mice exposed to cigarette smoke. The regulation of Rtp801 expression by cigarette smoke may rely on oxidative stress–dependent activation of the CCAAT response element in its promoter. We also found that Rtp801 was necessary and sufficient for nuclear factor-κB (NF-κB) activation in cultured cells and, when forcefully expressed in mouse lungs, it promoted NF-κB activation, alveolar inflammation, oxidative stress and apoptosis of alveolar septal cells. In contrast, Rtp801 knockout mice were markedly protected against acute cigarette smoke–induced lung injury, partly via increased mTOR signaling, and, when exposed chronically to cigarette smoke, against emphysema. Our data support the notion that Rtp801 may represent a major molecular sensor and mediator of cigarette smoke–induced lung injury.

Total face, double jaw, and tongue transplantation: An evolutionary concept

Background: The central face high-energy avulsive injury has been frequently encountered and predictably managed at the R Adams Cowley Shock Trauma Center. However, despite significant surgical advances and multiple surgical procedures, the ultimate outcome continues to reveal an inanimate, insensate, and suboptimal aesthetic result. Methods: To effectively address this challenging deformity, a comprehensive multidisciplinary approach was devised. The strategy involved the foundation of a basic science laboratory, the cultivation of a supportive institutional clinical environment, the innovative application of technologies, cadaveric simulations, a real-time clinical rehearsal, and an informed and willing recipient who had the characteristic deformity. Results: After institutional review board and organ procurement organization approval, a total face, double jaw, and tongue transplantation was performed on a 37-year-old man with a central face high-energy avulsive ballistic injury. Conclusions: This facial transplant represents the most comprehensive transplant performed to date. Through a systematic approach and clinical adherence to fundamental principles of aesthetic surgery, craniofacial surgery, and microsurgery and the innovative application of technologies, restoration of human appearance and function for individuals with a devastating composite disfigurement is now a reality. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.

Total face, double jaw, and tongue transplant simulation: a cadaveric study using computer-assisted techniques.

Background: With the transplantation of more extensive facial vascularized composite allografts, fundamental craniofacial and aesthetic principles become increasingly important. In addition, computer-assisted planning and intraoperative navigation may improve precision and efficiency in these complex procedures. Methods: Ten mock face transplants were performed in 20 cadavers. The vascularized composite allograft consisted of all facial skin, mimetic muscles, the tongue, the midface by means of a Le Fort III osteotomy, and the mandible by means of sagittal split osteotomies. Craniofacial computed tomographic scans were obtained before and after the mock transplants. Surgical planning software was used to virtually plan the osteotomies, and a surgical navigation system guided the osteotomies intraoperatively. Cephalometric analyses were compared between the virtually planned transplants and the actual postoperative results. Results: The combination of preoperative computerized planning and intraoperative guidance consistently produced a vascularized composite allograft that could be easily fixated to the prepared recipient, with only minimal burring of osteotomy sites necessary. Satisfactory occlusion was maintained, and postoperative computed tomography confirmed accurate skeletal fixation. Insignificant differences with regard to cephalometric analyses were noted when predicted and actual postoperative data were compared. Conclusions: The authors’ experience treating severe craniofacial injury allowed consistent transfer of facial vascularized composite allografts, maintaining proper occlusion. Preoperative computer planning and intraoperative navigation ensured precise osteotomies and a good donor-recipient skeletal match, which greatly reduced the need for intraoperative adjustments and manipulation. This total facial vascularized composite allograft represents one of the most extensive described and is intended to represent a typical central facial demolition pattern.

Total face, double jaw, and tongue transplant research procurement: an educational model.

Background: Transplantation of a facial vascularized composite allograft is a highly complex procedure that requires meticulous planning and affords little room for error. Although cadaveric dissections are an essential preparatory exercise, they cannot simulate the true clinical experience of facial vascularized composite allograft recovery. Methods: After obtaining institutional review board approval to perform a facial vascularized composite allograft research procurement, a 66-year-old, brain-dead donor was identified. The family graciously consented to donation of a total face, double jaw, and tongue allograft and multiple solid organs. Results: A craniofacial computed tomographic angiogram was obtained preoperatively to define the vascular anatomy and facilitate virtual computerized surgical planning. The allograft was procured in 10 hours, with an additional 2 hours required for an open tracheostomy and silicone facial impression. The donor was coagulopathic throughout the recovery, resulting in an estimated blood loss of 1500 ml. Fluorescence angiography confirmed adequate perfusion of the entire allograft based on lingual and facial arterial and external jugular and thyrolinguofacial venous pedicles. The solid organ transplant team initiated abdominal organ isolation while the facial allograft procurement was in progress. After completion of allograft recovery, the kidneys and liver were recovered without complication. Conclusions: Before conducting a clinical face transplant, adequate preparation is critical to maximize vascularized composite allotransplantation outcomes and preserve solid organ allograft function. As more centers begin to perform facial transplantation, research procurement of a facial vascularized composite allograft offers a unique educational opportunity for the surgical and anesthesia teams, the organ procurement organization, and the institution. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.

Found in space: Computer-assisted orthognathic alignment of a total face allograft in six degrees of freedom

PURPOSE Full facial osteomyocutaneous transplantation requires correct 3-dimensional (3D) alignment of donor osseous structures to a new cranial base with minimal reference points and 6 degrees of potential movement. We investigated whether computer-assisted design and manufacturing (CAD/CAM) could enable accurate placement of the facial skeleton. MATERIALS AND METHODS A prospective single-cohort study of Le Fort III-based maxillary-mandibular segment allotransplantation was performed in 5 cadaver pairs and 1 clinical pair. The osteotomies were modeled using computed tomography (CT) data and 3D modeling software and then translated to the donor-recipient pairs using surgical navigation and osteotomy cutting guides. The predicted values were calculated about all rotational axes (pitch, yaw, and roll) and along all translational axes (vertical, horizontal, and anteroposterior) and used as the independent variable. The primary outcome variable of the actual postoperative CT values was compared for fidelity to the prediction using the intraclass correlation coefficient (ICC). The similarity to the donor versus recipient values was calculated as a secondary independent variable, and both predicted and actual measurements were compared with it as a percentage. RESULTS The postoperative fidelity to the plan was adequate to excellent (ICC 0.520 to 0.975) with the exception of lateral translation (2.94 ± 1.31 mm predicted left vs 3.92 ± 2.17 mm right actual displacement; ICC 0.243). The predicted and actual values were not consistently skewed toward the donor or recipient values. CONCLUSIONS We have demonstrated a novel application of CAD/CAM that enables orthognathic alignment of a maxillary-mandibular segment to a new cranial base. Quantification of the alignment in all 6 degrees of freedom delivers precise control compared with the planned changes and allows postoperative quality control.

Optical Coherence Tomography Imaging as a Quality Assurance Tool for Evaluating Endoscopic Harvest of the Radial Artery

BACKGROUND Concerns about intimal disruption and spasm have limited enthusiasm for endoscopic radial artery harvest (ERAH), although the risk of these problems after this procedure remains uncertain. Radial artery conduits were screened intraoperatively before and after ERAH vs open harvest using catheter-based high-resolution optical coherence tomography (OCT) imaging. METHODS Twenty-four cadavers and 60 coronary artery bypass graft (CABG) patients scheduled to receive a RA graft underwent OCT imaging before (in situ) and after (ex vivo) open harvest or ERAH. Spasm was quantified by the percentage change in luminal volume between images. Intimal disruption was classified as minor or severe depending on whether the defect was confined to branch ostia or involved the luminal surface. Histology was used to confirm OCT findings. RESULTS Luminal volume significantly declined after harvest in all RAs from CABG patients, but there was no difference between groups: -43% +/- 29% vs -35% +/- 38% change after ERAH (n = 21) vs open harvest (n = 39; p = 0.342). Significantly more intimal injury was noted after ERAH vs open harvest (34/41 vs 9/43, intimal tears/total evaluated RAs, p < 0.0001). Most intimal injury was minor: only 2 tears involved the luminal surface of the RA (both after ERAH). Serial imaging in cadavers revealed that 86% of ostial tears occur in ERAH during the initial blunt dissection step using the endoscope. CONCLUSIONS Although branch injury is a pitfall of ERAH, OCT imaging documented that the quality of RA procured is acceptable and comparable with open harvest. Catheter-based OCT provides an important quality assurance tool for RA harvest.

Thinking inside the graft: applications of optical coherence tomography in coronary artery bypass grafting

Recent advances in catheter-based optical coherence tomography (OCT) have provided the necessary resolution and acquisition speed for high-quality intravascular imaging. Complications associated with clearing blood from the vessel of a living patient have prevented its wider acceptance. We identify a surgical application that takes advantage of the vascular imaging powers of OCT but that circumvents the difficulties. Coronary artery bypass grafting (CABG) is the most commonly performed major surgery in America. A critical determinant of its outcome has been postulated to be injury to the conduit vessel incurred during the harvesting procedure or pathology preexistent in the harvested vessel. As a test of feasibility, intravascular OCT imaging is obtained from the radial arteries (RAs) and/or saphenous veins (SVs) of 35 patients scheduled for CABG. Pathologies detected by OCT are compared to registered histological sections obtained from discarded segments of each graft. OCT reliably detects atherosclerotic lesions in the RAs and discerns plaque morphology as fibrous, fibrocalcific, or fibroatheromatous. OCT is also used to assess intimal trauma and residual thrombi related to endoscopic harvest and the quality of the distal anastomosis. We demonstrate the feasibility of OCT imaging as an intraoperative tool to select conduit vessels for CABG.

Algorithm for Total Face and Multiorgan Procurement From a Brain‐Dead Donor

Procurement of a facial vascularized composite allograft (VCA) should allow concurrent procurement of all solid organs and ensure their integrity. Because full facial procurement is time–intensive, “simultaneous–start” procurement could entail VCA ischemia over 12 h. We procured a total face osteomyocutaneous VCA from a brain–dead donor. Bedside tracheostomy and facial mask impression were performed preoperative day 1. Solid organ recovery included heart, lungs, liver, kidneys, and pancreas. Facial dissection time was 12 h over 15 h to diminish ischemia while awaiting recipient preparation. Solid organ recovery began at 13.5 h, during midfacial osteotomies, and concluded immediately after facial explantation. Facial thoracic and abdominal teams worked concurrently. Estimated blood loss was 1300 mL, requiring five units of pRBC and two units FFP. Urine output, MAP, pH and PaO2 remained normal. All organs had good postoperative function. We propose an algorithm that allows “face first, concurrent completion” recovery of a complex facial VCA by planning multiple pathways to expedient recovery of vital organs in the event of clinical instability. Beginning the recipient operation earlier may reduce waiting time due to extensive recipient scarring causing difficult dissection.

Harmonic scalpel versus electrocautery for harvest of radial artery conduits: Reduced risk of spasm and intimal injury on optical coherence tomography

OBJECTIVE Vasospasm is the primary obstacle to widespread adoption of the radial artery as a conduit in coronary artery bypass grafting. We used optical coherence tomography, a catheter-based intravascular imaging modality, to measure the degree of radial artery spasm induced by means of harvest with electrocautery or a harmonic scalpel in patients undergoing coronary artery bypass grafting. METHODS Radial arteries were harvested from 44 consecutive patients with a harmonic scalpel (n = 15) or electrocautery (n = 29). Vessels were imaged before harvesting and after removal from the arm, with saphenous vein tracts serving as internal controls. Optical coherence tomographic findings for the degree of harvesting-induced injury were validated against histologic measures. RESULTS Optical coherence tomographic measures of endovascular dimensions and injury correlated strongly with histologic findings. Mean luminal volume, a measure of vasospasm, decreased significantly less after harvesting with a harmonic scalpel (9% +/- 7%) than with electrocautery (35% +/- 6%, P = .015). Completely intact intima was present in 11 (73%) of 15 radial arteries harvested with a harmonic scalpel (73%) compared with 9 of 29 arteries harvested by means of electrocautery (31%, P = .011). Intraoperative flow measurements and patency rates at 5 days postoperatively were not significantly different among groups. CONCLUSIONS Optical coherence tomography provides a level of speed and accuracy for quantifying endothelial injury and vasospasm that has not been described for any other modality, suggesting potential as an intraoperative quality assurance tool. Our optical coherence tomographic findings suggest that the harmonic scalpel induces less spasm and intimal injury compared with electrocautery.

Surface anatomy of the middle division of the facial nerve: Zuker's point.

Background: The anatomy of the facial nerve and its branches has been well documented. The course of the extratemporal facial nerve, its anatomical planes, and the surface landmarks of the temporal division and marginal mandibular division are well known. However, the surface landmark of the middle division of the facial nerve has not been studied to date. Methods: Eighteen hemifacial dissections in 10 fresh human cadavers were performed through a preauricular face-lift incision. An 18-gauge needle with brilliant green dye was used to mark the nerve through the skin before dissection. The exact location of the middle division branches of the facial nerve was documented in relation to the transcutaneous marking. Results: The middle division branches of the facial nerve were found to lie at a mean of 2.3 mm from the tattooed point, with a range of 0 to 6 mm. A nerve branch was found directly tattooed by the needle seven of 18 times, inferior to the tattoo five of 18 times, and superior to the tattoo six of 18 times. Conclusions: The zygomatic/buccal motor branch that innervates the zygomaticus major muscle can be reliably found at the midway point on a line drawn from the root of the helix and the lateral commissure of the mouth. This study will help guide surgeons to the middle division of the facial nerve as it applies to facial surgery.