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For some patients who have lost the lower part of an arm, hand transplant offers the possibility of receiving a new limb with varying degrees of sensation and function. This procedure, Vascularized Composite Allotransplantation (VCA), is demanding for patients and their care community and comes with significant risks. As a high-stakes decision, patients interested in VCA are subject to extensive clinical evaluation and eligibility decision making. Patients and their care community must also decide if hand transplant (versus other approaches including rehabilitative therapies with or without prosthesis) is right for them. This decision making is often confusing and practically and emotionally fraught. It is complicated in four ways: by the numerous beneficial and harmful potential effects of hand transplant or other options, the number of people affected by VCA and the diverse or conflicting positions that they may hold, the practical demands and limitations of the patient's life situation, and the existential significance of limb loss and transplant for the patient's being. Patients need support in working through these treatment determining issues. Evaluation does not provide this support. Shared decision making (SDM) is a method of care that helps patients think, talk, and feel their way through to the right course of action for them. However, traditional models of SDM that focus on weighing possible beneficial and harmful effects of treatments are ill-equipped to tackle the heterogeneous issues of VCA. A recent model, Purposeful SDM extends the range of troubling issues that SDM can help support beyond opposing effects, to include conflicting positions, life situations, and existential being. In this paper we explore the pertinence of these issues in VCA, methods of SDM that each require of clinicians, the benefits of supporting patients with the breadth of issues in their unique problematic situations, implications for outcomes and practice, and extend the theory of the Purposeful SDM model itself based on the issues present in hand transplant decision making.

Face transplantation became a reality with the first case performed in 2005. Facial tissue allograft procurement is technically complex and time-intensive. Brain-dead deceased donors are frequently, if not always, multiorgan donors. Every effort should be made during face allograft recovery to minimize any risk to the recovery of lifesaving solid organs. Some programs require the procurement of a myofascial vascularized skin graft to function as a sentinel flap allowing frequent monitoring for rejection without negatively impacting the esthetics of the face graft. Up till now, the flap used has been the radial forearm flap. Procuring the radial forearm flap places the procuring team in close proximity to the head and torso, where the face recovery and the solid organ recovery teams would require unhindered access. Here, we present the posterior tibial artery flap as an alternative flap that would provide benefits to the coordination of the multiple teams working to procure organs from a deceased donor.

Background:. Dynamic facial reanimation is the gold standard treatment for a paralyzed face. The use of the cross-face nerve graft (CFNG) in combination with the masseteric nerve to innervate the free gracilis muscle has been reported to provide both spontaneity and strong neural input. We report a case series of dual innervation, using a novel method where the branch to masseter is coapted to the side of the CFNG. Methods:. Eight patients received free gracilis muscle transfer using the new dual innervation method between September 2014 and December 2017. The CFNG, which was performed nine months prior, was sutured in an end-to-end fashion to the obturator nerve. A nerve graft was coapted to the ipsilateral masseteric nerve and then sutured in an end-to-side fashion to the CFNG proximal to its coaptation to the obturator nerve. Results:. All patients recovered smile function with and without teeth clenching around the same time period. Smiles without teeth clenching appeared later in two of eight patients and earlier in one of eight patients, being noted at an average of 8.25 months of follow-up versus 7.6 months. The estimate of true attainment is limited by the spacing of follow-up dates. Average follow-up time was 36.07 months (range: 10–71.5). FACE-Gram software smile analysis with and without biting demonstrated similar excursion on average (7.64 mm versus 8.6 mm respectively, P = 0.93), both of which are significantly improved from preoperation. Conclusion:. This novel method of a dual-innervated free gracilis muscle transfer offers a viable technique that achieves a symmetric, strong, and emotional smile.

Summary:. After a transnasal endoscopic resection of a high-grade adenoid cystic carcinoma that underwent adjuvant chemoradiation, there was delayed recurrence managed by en bloc resection through an open craniofacial approach. Subsequently, the patient developed a chronic nasocranial fistula with secondary infection and bone flap resorption. This resulted in infectious episodes with secondary scalp incisional dehiscence and hardware exposure which required multiple bone debridement procedures, hardware removal, prolonged IV antibiotics, and hyperbaric oxygen treatment. The nasocranial fistula and chronic frontal bone osteomyelitis persisted despite the previous interventions. The patient underwent a frontal bone removal and obliteration of the anterior cranial base fistula with a free vastus lateralis muscle flap. At 4 weeks postoperatively, the intranasal portion of the muscle flap had completely mucosalized. After a 6-week course of IV antibiotics, a secondary cranioplasty using a custom-made poly-ether-ether-ketone implant was performed. The patient remained disease- and infection-free for the duration of follow-up (17 months).

Background:. Nerve transfer from the masseteric branch of the trigeminal nerve is a widely performed procedure for facial reanimation. Despite achieving powerful muscle force, clinical and aesthetic results leave room for improvement. Preclinical animal models are invaluable to establishing new therapeutic approaches. This anatomical study aimed to establish a masseteric-to-zygomatic nerve transfer model in rats and pigs. Methods:. The masseteric branch of the trigeminal nerve and the zygomatic branch of the facial nerve were dissected in 30 swine and 40 rat hemifaces. Both nerves were mobilized and approximated to achieve an overlap between the nerve ends. Over the course of dissecting both nerves, their anatomy, length, and branching pattern were documented. At the coaptation point, diameters of both nerves were measured, and samples were taken for neuromorphometric analysis. Results:. Anatomic details and landmarks were described. Tension-free coaptation was possible in all rat and pig dissections. In rats, the masseteric branch had an average diameter of 0.36 mm (±0.06), and the zygomatic branch average diameter was 0.46 mm (±0.13). In pigs, the masseteric branch measured 0.52 (±0.16) mm and the zygomatic branch, 0.59 (±0.16) mm. No significant differences were found between the diameters and axon counts of both nerves in pigs. In rats, however, their diameters, axon counts, and fascicular areas were significantly different. Conclusion:. Our study demonstrated the feasibility of direct masseteric-to-zygomatic nerve transfer in rats and pigs and provided general anatomic knowledge of both nerves.

Summary:. The latissimus dorsi muscle is the workhorse flap for intrathoracic reconstruction. Prior thoracotomy, which divides the latissimus dorsi muscle, limits the muscle’s intrathoracic reach. We present our experience using the distal portion of the muscle for intrathoracic reconstruction based off an intercostal vessel. We also demonstrate the ability of this intercostal perforator to allow for chimeric flap elevation with a separate skin paddle, depending on the branching pattern of the intercostal vessels. This study provides a case series of three consecutive patients, treated between September 2021 and June 2022. The intrathoracic pathology addressed in these patients are bronchopleural fistula, aortoesophageal fistula, and bronchoesophageal fistula. All patients had the resolution of symptoms related to intrathoracic fistulae and did not experience recurrence. This novel pedicled muscle flap can be an additional option for patients with prior thoracotomy and avoids the morbidity which can be seen with the serratus or rectus abdominis muscle flaps.

Abstract Background Genomics enables individualized diagnosis and treatment, but large challenges remain to functionally interpret rare variants. To date, only one causative variant has been described for KCNK9 imprinting syndrome (KIS). The genotypic and phenotypic spectrum of KIS has yet to be described and the precise mechanism of disease fully understood. Methods This study discovers mechanisms underlying KCNK9 imprinting syndrome (KIS) by describing 15 novel KCNK9 alterations from 47 KIS-affected individuals. We use clinical genetics and computer-assisted facial phenotyping to describe the phenotypic spectrum of KIS. We then interrogate the functional effects of the variants in the encoded TASK3 channel using sequence-based analysis, 3D molecular mechanic and dynamic protein modeling, and in vitro electrophysiological and functional methodologies. Results We describe the broader genetic and phenotypic variability for KIS in a cohort of individuals identifying an additional mutational hotspot at p.Arg131 and demonstrating the common features of this neurodevelopmental disorder to include motor and speech delay, intellectual disability, early feeding difficulties, muscular hypotonia, behavioral abnormalities, and dysmorphic features. The computational protein modeling and in vitro electrophysiological studies discover variability of the impact of KCNK9 variants on TASK3 channel function identifying variants causing gain and others causing loss of conductance. The most consistent functional impact of KCNK9 genetic variants, however, was altered channel regulation. Conclusions This study extends our understanding of KIS mechanisms demonstrating its complex etiology including gain and loss of channel function and consistent loss of channel regulation. These data are rapidly applicable to diagnostic strategies, as KIS is not identifiable from clinical features alone and thus should be molecularly diagnosed. Furthermore, our data suggests unique therapeutic strategies may be needed to address the specific functional consequences of KCNK9 variation on channel function and regulation.

The application of autologous fat grafting in reconstructive surgery is commonly used to improve functional form. This review aims to provide an overview of the scientific evidence on the biology of adipose tissue, the role of adipose-derived stem cells, and the indications of adipose tissue grafting in peripheral nerve surgery. Adipose tissue is easily accessible through the lower abdomen and inner thighs. Non-vascularized adipose tissue grafting does not support oxidative and ischemic stress, resulting in variable survival of adipocytes within the first 24 hours. Enrichment of adipose tissue with a stromal vascular fraction is purported to increase the number of adipose-derived stem cells and is postulated to augment the long-term stability of adipose tissue grafts. Basic science nerve research suggests an increase in nerve regeneration and nerve revascularization, and a decrease in nerve fibrosis after the addition of adipose-derived stem cells or adipose tissue. In clinical studies, the use of autologous lipofilling is mostly applied to secondary carpal tunnel release revisions with promising results. Since the use of adipose-derived stem cells in peripheral nerve reconstruction is relatively new, more studies are needed to explore safety and long-term effects on peripheral nerve regeneration. The Food and Drug Administration stipulates that adipose-derived stem cell transplantation should be minimally manipulated, enzyme-free, and used in the same surgical procedure, e.g. adipose tissue grafts that contain native adipose-derived stem cells or stromal vascular fraction. Future research may be shifted towards the use of tissue-engineered adipose tissue to create a supportive microenvironment for autologous graft survival. Shelf-ready alternatives could be enhanced with adipose-derived stem cells or growth factors and eliminate the need for adipose tissue harvest.

Purpose: Examining the outcomes and progression of face transplants has expanded to include the recent advancements in artificial intelligence. This novel methodology has allowed for the objective exploration of emotional expression. To our knowledge, this examined emotional expression has yet to be correlated to the hypothesized functioning of the allograft. We have combined the result of the AI software with a software analyzing smile excursion; demonstrating the progression of the allograft in our face transplant patient. This study helps illuminate the software possibilities for objective measures in transplant progression. Methods: Images were analyzed from our face transplant patient post-operatively at approximately 6-month intervals for four years. The still images for each time interval include both a neutral facial expression and a full-face smile with teeth. The images were taken from video clips of the patient and then analyzed using the FACEgram software (Hadlock & Urban, 2012). The measurements of the smile excursion were standardized based off of the pupil diameter and excursion was measured relative to the neutral expression of each time period. The emotional expression data was acquired using FaceReader AI software from Noldus Information Technology (Wageningen, The Netherlands). The emotional analysis was done on 2 second clips from clinical videos of the patient, the same videos used for the still images. This data was correlated with the smile excursion measurements. Results: The post-operative smile excursion analysis from 6 to 49 months demonstrated a near double in smile excursion from 3.58mm to 6.04mm. The smile excursion data has a squared correlation of 0.705; a strong upward linear trend of excursion. From 6 to 35 months, the happy emotion increased gradually from 0% to 15.8% (49-month data unavailable). Performed correlative analysis showed a positive correlation coefficient of 0.63. This moderate to strong correlation demonstrates the intuitive relationship of happy emotion and lip excursion during full face smiling. The findings also substantiate the AI software’s detection of increasing activity in the lip corner puller action unit from zero to 3/5 intensity over the same period. Conclusion: This study demonstrates the correlation of smile excursion to happy emotional expression in our face transplant patient. The correlation square of the lip excursion shows a trend of increased functioning of the allograft over time; substantiating the AI’s finding. This data provides evidence for the use of artificial intelligence as a measure of transplant strength progression. The conjoined analysis of patient images and videos has supported proof for the ability to analyze transplant healing progression and efficacy in an objective form. Hadlock, T. A., & Urban, L. S. (2012). Toward a Universal, Automated Facial Measurement Tool in Facial Reanimation. Archives of Facial Plastic Surgery,14(4). doi:10.1001/archfacial.2012.111

OBJECTIVES/GOALS: Virtual surgical planning and 3D printing enable streamlined surgeries and increased complexity. These technologies, however, require CT scans and radiation exposure. This project’s goal is to optimize and demonstrate the accuracy of Black Bone MRI for surgical planning in reconstructive surgery. METHODS/STUDY POPULATION: Four common craniofacial surgeries were planned and performed on cadaver specimens (maxillary advancement, orbital floor reconstruction with patient-specific implants, cranial vault reconstruction, and fibular free flap reconstruction of the mandible). For each surgical procedure, ten cadaver heads were used. Five of each surgery were planned and 3D printed guides were created utilizing Black Bone MRI versus five with CT scans. Following mock surgeries, all specimens underwent a post-operative CT scan. 3d reconstruction was performed and surgical accuracy compared to the plan was assessed using GeoMagic Wrap, assessing average post-operative deviation from plan. RESULTS/ANTICIPATED RESULTS: In all surgeries, guides created from Black Bone MRI demonstrated high accuracy to surgical plan. Average osteotomy (cut) deviation from plan was not statistically significantly different when Black Bone MRI was used compared to CT scans for planning and guide creation in the wide variety of craniofacial surgeries performed. The average deviation of post-operative anatomy from pre-operative plan was also not statistically significant when Black Bone MRI versus CT scans were utilized in the surgeries. These results then enabled the translational application of this technology clinically, and we demonstrate a clinical reconstructive craniofacial case planned utilizing Black Bone MRI. DISCUSSION/SIGNIFICANCE OF IMPACT: This study demonstrates that virtual surgical planning and 3d surgical guide creation can be performed using Black Bone MRI with comparable accuracy to CT scans in a wide variety of craniofacial procedures. This could dramatically reduce radiation exposure for patients. The successful segmentation, virtual planning, and 3d printing of accurate guides from Black Bone MRI demonstrate potential to change the pre-operative planning standard of care. This project, overall, also demonstrates the development of new solutions to advance clinical care, thus serving as an example of moving translational science from a concept to the operating room.

OBJECTIVES/GOALS: Face transplant can offer functional and aesthetic restoration to patients who have exhausted reconstructive options. Ethical issues in face transplant still abound, including that of patient selection. The goal of this study was to assess ethicists’ viewpoints on face transplant. METHODS/STUDY POPULATION: A large-scale online survey of attendees of the International Conference on Clinical Ethics Consultation (N = 401) was performed to assess ethicists’ opinions on issues in face transplant. Questions were asked regarding the risk-benefit ratio of immunosuppression, permissibility of face transplant for more recipient subpopulations (including children and blind patients), donor-recipient age, gender, and ethnicity mismatches, and ethics committee make-up. RESULTS/ANTICIPATED RESULTS: Among 84 respondents, 84% agreed it is permissible to perform a face transplant on an adult with no medical contraindications. The majority of respondents agreed that it is permissible to perform a face transplant on a child or blind recipient. An issue of continued concern was risk of immunosuppression. Respondents had a high threshold of permissibility for ethnic mismatches between donor and recipient, and 43% reported it is permissible to have a gender mismatch. A 10 year age difference between donor and recipient was the most commonly accepted. Questions regarding the ideal composition of a face transplant ethics committee demonstrated consensus on the roles that should be represented. DISCUSSION/SIGNIFICANCE OF IMPACT: This study provides insight into ethicists’ viewpoints on face transplant, which demonstrates a high level of permissibility towards the procedure. This may be due to the early success of face transplants and the shifting ethical issues in the field to practical aspects of the procedure. This research also provides guidance to programs regarding questions of donor and recipient selection, ethics committee composition, and offers insight into strengthening the ethical framework of the field.

OBJECTIVES/GOALS: This study’s goal is to determine whether intraoperative treatment of facial nerves with polyethylene glycol (PEG) fusion technology improves facial paralysis outcomes. Improved facial nerve regeneration in facial paralysis patients would lead to improved recovery time and effectiveness. METHODS/STUDY POPULATION: 30 rats were utilized; 15 underwent facial nerve regeneration without PEG fusion, and 15 with PEG fusion. Facial paralysis was initiated on the left by transection of the buccal and marginal mandibular branches of facial nerve. The buccal branch was repaired though microsuture technique. Neurorrhaphy sites of rats in the PEG group were exposed to calcium free saline, methylene blue, and polyethylene glycol. Nerve continuity was assessed post-operative in 5 animals in each group through electron microscopy. Functionality was assessed in the other 10 per group by EMG and whisker analysis after surgery, and weekly for 8 weeks. At 8 weeks, nerves and distal muscles were histologically analyzed. RESULTS/ANTICIPATED RESULTS: PEG fusion technology immediately restored axonal continuity following surgery, demonstrated by electron microscopy. Electrophysiology was also similarly restored across the site immediately, determined through intraoperative nerve stimulation, in the PEG fusion group. The nonintervention group showed dramatically reduced functional recovery than the PEG fusion group following surgery, shown by lower whisking activity and poor electrophysiology outcomes. Furthermore, the PEG fusion group showed statistically significant higher fascicle counts, myelination diameter, axonal diameter, and distal muscle fibers histologically. DISCUSSION/SIGNIFICANCE OF IMPACT: This study demonstrates that polyethylene fusion technology may improve facial reanimation outcomes. PEG is already a FDA-approved drug, and thus the pathway to translational clinical application of this work may thus be streamlined, bringing new options to patients with facial paralysis.