Establishing an upper extremity transplantation program: lessons learnt over 12 years.

PURPOSE OF REVIEW: As one of the early hand transplant programs in the world, we are often asked to educate other programs on the lessons we have learned and on how to set up a successful hand transplantation program. RECENT FINDINGS: Two decades of global experience with vascularized composite allotransplantation (VCA) of the upper limb have demonstrated improved functional outcomes and quality of life for carefully screened patients. Despite initial reticence about VCA, over 30 patients in the USA have benefited from hand transplantation, with around 80% long-term successes. We have experience with four bilateral upper extremity patients who have undergone bilateral upper extremity allotransplants. This review article highlights our personal experience and lessons with respect to VCA team assembly, logistics, patient selection, perioperative planning, the operative procedure, and postoperative management. SUMMARY: Continual learning and critical evaluation are crucial to maintaining a successful upper extremity VCA program. This will ensure that patients who stand to benefit most from this life-enhancing procedure are identified and are others optimized to achieve the best possible outcomes.

Evaluation of Long-Term Surgical and Patient-Reported Outcomes after Pediatric Facial Reanimation.

BACKGROUND: Outcomes of pediatric facial reanimation beyond 10 years are not known. This cross-sectional study evaluated long-term surgical and patient-reported outcomes of adults who underwent smile reconstruction as children with either a cross-face nerve graft (CFNG) or masseter nerve transfer at least 10 years previously. METHODS: Commissure excursion was quantified with FACE-Gram software at 3 time points: preoperatively, early postoperatively within 2 years, and at long-term follow-up. Patient-reported outcomes were evaluated with validated questionnaires (Facial Clinimetric Evaluation Scale, FACE-Q 1.0) and thematic analysis of semistructured interviews. Results are reported as median (interquartile range [IQR]). RESULTS: A total of 42 patients were included (26 women and 16 men). Median long-term follow-up was 19.3 years (IQR, 8.8 years) for CFNG and 17.6 years (IQR, 5.8 years) for masseter nerve transfer. For both groups, commissure excursion increased significantly from preoperative to early postoperative time points and remained stable at long-term follow-up (P < 0.0001). Commissure excursion at long-term follow-up between the 2 groups was not significantly different (CFNG, 5.0 mm [IQR, 9.4 mm]; masseter nerve transfer, 8.4 mm [IQR, 4.1 mm]); P > 0.05). For patient-reported outcomes, median Facial Clinimetric Evaluation Scale score was 72 of 100, and 95% of respondents agreed with the statement "I am pleased with the result" on the FACE-Q 1.0. Overall quality of life was rated at 7 of 10 or greater by 97% of participants, and all participants would recommend the surgery to other children. CONCLUSIONS: Pediatric facial reanimation with CFNG or masseter nerve transfer reliably improves commissure excursion with longevity beyond 10 years. Adult patients report overall high satisfaction and social functioning.

The Nuances of Hand Transplantation After Sepsis.

Vascularized composite allotransplantation (VCA) of the upper extremity is an established restorative procedure for selected patients with acquired upper limb loss. The majority of upper limb VCAs performed worldwide have been for victims of various forms of trauma. However, in the developed world, amputation following severe sepsis seems to be an increasingly common indication for referral to hand transplant programs. Unlike trauma patients with isolated limb injuries, patients with amputations as a complication of sepsis have survived through a state of global tissue hypoperfusion and multisystem organ failure with severe, enduring effects on the entire body's physiology. This article reviews the unique considerations for VCA candidacy in postsepsis patients with upper limb amputation. These insights may also be relevant to postsepsis patients undergoing other forms of transplantation or to VCA patients requiring additional future solid organ transplants.

Surgery for internal rotation contracture in infancy may obviate the need for brachial plexus nerve reconstruction: early experience.

BACKGROUND: Shoulder internal rotation contracture and subluxation in the first year of life has long been recognized in some patients with brachial plexus birth injury (BPBI). Surgical management of shoulder pathology has traditionally been undertaken following nerve reconstruction as necessary. In some patients; however, shoulder pathology may impair or obscure functional neuromuscular recovery of the upper extremity. As a proof of concept, we report a highly selected subset of patients with BPBI in whom shoulder surgery undertaken before one year of age obviated the need for neuroma resection and nerve grafting. METHODS: A retrospective review was performed of all patients with upper trunk BPBI who underwent shoulder surgery before one year of age from 2015 to 2018. Upper extremity motor function was evaluated with preoperative and postoperative Active Movement Scale scores, Cookie tests, and the requirement for subsequent neuroma resection and nerve grafting. RESULTS: Fifteen patients with BPBI meeting the inclusion criteria underwent shoulder surgery (including a subscapularis slide and tendon transfers of the teres major and latissimus dorsi muscles) before 1 year of age. Preoperatively, no patients of the appropriate age passed the Cookie test for elbow flexion. Thirteen patients either passed the Cookie test or scored Active Movement Scale score 7 for elbow flexion at or before the last available follow-up undertaken at a median age of 3.4 [1.4, 5.2] years. One of those 13 patients underwent single fascicular distal nerve transfer to improve elbow flexion before subsequently passing the Cookie test. Two patients did not have sufficient follow-up to assess elbow flexion. CONCLUSION: Although the exact role of shoulder surgery in infancy for BPBI remains to be defined, the findings from this study provide proof of concept that early, targeted surgical treatment of the shoulder may obviate the need for brachial plexus nerve reconstruction in a highly selected group of infants with BPBI.

Recent Advances in the Treatment of Brachial Plexus Birth Injury.

LEARNING OBJECTIVES: After studying this article, the participant should be able to: 1. Describe methods of clinical evaluation for neurologic recovery in brachial plexus birth injury. 2. Understand the role of different diagnostic imaging modalities to evaluate the upper limb. 3. List nonsurgical strategies and surgical procedures to manage shoulder abnormality. 4. Explain the advantages and disadvantages of microsurgical nerve reconstruction and distal nerve transfers in brachial plexus birth injury. 5. Recognize the prevalence of pain in this population and the need for greater sensory outcomes evaluation. SUMMARY: Brachial plexus birth injury (BPBI) results from closed traction injury to the brachial plexus in the neck during an infant's vertex passage through the birth canal. Although spontaneous upper limb recovery occurs in most instances of BPBI, some infants do not demonstrate adequate motor recovery within an acceptable timeline and require surgical intervention to restore upper limb function. This article reviews major advances in the management of BPBI in the past decade that include improved understanding of shoulder pathology and its impact on observed motor recovery, novel surgical techniques, new insights in sensory function and pain, and global efforts to develop standardized outcomes assessment scales.

Psychosocial predictors in upper-extremity vascularized composite allotransplantation: A qualitative study of multidimensional experiences including patients, healthcare professionals, and close relatives.

Background: The impact of patient-specific psychosocial factors on functional outcomes after upper-extremity (UE) vascularized composite allotransplantation (VCA) is poorly understood. The objective of this study was to identify relevant psychosocial predictors for success or failure of UE VCA in an Austrian cohort. Methods: A qualitative study was undertaken consisting of semi-structured interviews with UE VCA staff, transplanted patients, and close relatives. Participants were asked about their perceptions of factors that either favored or hindered a successful transplant outcome, including functional status before surgery, preparation for transplant, decision-making, rehabilitation and functional outcome after surgery, and family and social support. Interviews were conducted online and recorded with the consent of interviewees. Results: Four bilateral UE VCA patients, 7 healthcare professionals, and a sister of a patient participated in the study. Thematic analysis revealed the importance of an expert interdisciplinary team with adequate resources for patient selection. Psychosocial aspects of prospective candidates are crucial to evaluate as they contribute to success. Both patients and providers may be impacted by public perceptions of UE VCA. Functional outcomes are optimized with a life-long commitment to rehabilitation as well as close, ongoing provider involvement. Conclusion: Psychosocial factors are important elements in the assessment and follow-up care for UE VCA. To best capture psychosocial elements of care, protocols must be individualized, patient-centered, and interdisciplinary. Investigating psychosocial predictors and collecting outcomes is, thus, critical to justifying UE VCA as a medical intervention and to providing accurate and salient information to prospective candidates.

Dynamic Reconstruction of Facial Paralysis in Craniofacial Microsomia.

BACKGROUND: Craniofacial microsomia is associated with maxillomandibular hypoplasia, microtia, soft-tissue deficiency, and variable severity of cranial nerve dysfunction, most often of the facial nerve. This study evaluated the incidence of facial paralysis in patients with craniofacial microsomia and outcomes after free functioning muscle transfer for dynamic smile reconstruction. METHODS: A single-center, retrospective, cross-sectional study was performed from 1985 to 2018 to identify pediatric patients with craniofacial microsomia and severe facial nerve dysfunction who underwent dynamic smile reconstruction with free functioning muscle transfer. Preoperative and postoperative facial symmetry and oral commissure excursion during maximal smile were measured using photogrammetric facial analysis software. RESULTS: This study included 186 patients with craniofacial microsomia; 41 patients (21 male patients, 20 female patients) had documented facial nerve dysfunction (22 percent) affecting all branches (51 percent) or the mandibular branch only (24 percent). Patients with severe facial paralysis (n = 8) underwent smile reconstruction with a free functioning muscle transfer neurotized either with a cross-face nerve graft (n = 7) or with the ipsilateral motor nerve to masseter (n =1). All patients achieved volitional muscle contraction with improvement in lip symmetry and oral commissure excursion (median, 8 mm; interquartile range, 3 to 10 mm). The timing of orthognathic surgery and facial paralysis reconstruction was an important consideration in optimizing patient outcomes. CONCLUSIONS: The authors' institution's incidence of facial nerve dysfunction in children with craniofacial microsomia is 22 percent. Free functioning muscle transfer is a reliable option for smile reconstruction in children with craniofacial microsomia. To optimize outcomes, a novel treatment algorithm is proposed for craniofacial microsomia patients likely to require both orthognathic surgery and facial paralysis reconstruction. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Combined local delivery of tacrolimus and stem cells in hydrogel for enhancing peripheral nerve regeneration.

The application of scaffold-based stem cell transplantation to enhance peripheral nerve regeneration has great potential. Recently, the neuroregenerative potential of tacrolimus (a U.S. Food and Drug Administration-approved immunosuppressant) has been explored. In this study, a fibrin gel-based drug delivery system for sustained and localized tacrolimus release was combined with rat adipose-derived mesenchymal stem cells (MSC) to investigate cell viability in vitro. Tacrolimus was encapsulated in poly(lactic-co-glycolic) acid (PLGA) microspheres and suspended in fibrin hydrogel, using concentrations of 0.01 and 100 ng/ml. Drug release over time was measured. MSCs were cultured in drug-released media collected at various days to mimic systemic exposure. MSCs were combined with (i) hydrogel only, (ii) empty PLGA microspheres in the hydrogel, (iii) 0.01, and (iv) 100 ng/ml of tacrolimus PLGA microspheres in the hydrogel. Stem cell presence and viability were evaluated. A sustained release of 100 ng/ml tacrolimus microspheres was observed for up to 35 days. Stem cell presence was confirmed and cell viability was observed up to 7 days, with no significant differences between groups. This study suggests that combined delivery of 100 ng/ml tacrolimus and MSCs in fibrin hydrogel does not result in cytotoxic effects and could be used to enhance peripheral nerve regeneration.

Local FK506 drug delivery enhances nerve regeneration through fresh, unprocessed peripheral nerve allografts.

OBJECTIVE: Nerve allografts offer many advantages in the reconstruction of peripheral nerve gaps: they retain their native microstructure, contain pro-regenerative Schwann cells, are widely available, and avoid donor site morbidity. Unfortunately, clinical use of nerve allografts is limited by the need for systemic immunosuppression and its adverse effects. To eliminate the toxicity of the systemic immunosuppressant FK506, we developed a local FK506 drug delivery system (DDS) to provide drug release over 28 days. The study objective was to investigate if the local FK506 DDS enhances nerve regeneration in a rodent model of nerve gap defect reconstruction with immunologically-disparate nerve allografts. METHODS: In male Lewis rats, a common peroneal nerve gap defect was reconstructed with either a 20 mm nerve isograft from a donor Lewis rat or a 20 mm fresh, unprocessed nerve allograft from an immunologically incompatible donor ACI rat. After 4 weeks of survival, nerve regeneration was evaluated using retrograde neuronal labelling, quantitative histomorphometry, and serum cytokine profile. RESULTS: Treatment with both systemic FK506 and the local FK506 DDS significantly improved motor and sensory neuronal regeneration, as well as histomorphometric indices including myelinated axon number. Rats with nerve allografts treated with either systemic or local FK506 had significantly reduced serum concentrations of the pro-inflammatory cytokine IL-12 compared to untreated vehicle control rats with nerve allografts. Serum FK506 levels were undetectable in rats with local FK506 DDS. INTERPRETATION: The local FK506 DDS improved motor and sensory nerve regeneration through fresh nerve allografts to a level equal to that of either systemic FK506 or nerve isografting. This treatment may be clinically translatable in peripheral nerve reconstruction or vascularized composite allotransplantation.

Orbital Compartment Syndrome Following Major Burn Resuscitation: A Case Series and Survey of Practice Patterns.

Orbital compartment syndrome (OCS) is a rare but devastating complication of over-resuscitation in burn patients that may lead to permanent visual loss. The purpose of this study was to 1) present a series of burn patients with OCS and 2) survey practice patterns of monitoring intra-ocular pressure (IOP) during burn resuscitation. Cases of OCS at two American Burn Association (ABA)-verified burn centers were retrospectively reviewed. Patients were included if they 1) required lateral canthotomy/cantholysis for elevated IOPs or 2) developed blindness on admission unrelated to any other ocular pathology. Data were collected on demographics, burn characteristics, fluid administration, ophthalmologic findings, and complications. An eight-item electronic survey was distributed by email through the ABA to all physician members. Twelve patients with OCS were identified, with a mean age of 47.8 ± 12.4 years and TBSA of 63.7 ± 18.6%. Mean fluid resuscitation at 24 hours was 4.9 ± 1.6 ml/kg/%TBSA or 0.29 ± 0.06 liter/kg. Eight patients underwent canthotomy/cantholysis for OCS, whereas four were later found to have visual loss. A total of 83 (14%) ABA physicians responded to the survey. IOP was routinely measured by 23% of respondents during acute burn resuscitation. OCS appears to have developed despite a relatively low 24-hour ml/kg/% burn resuscitation volume, but with a relatively higher cumulative (liter/kg) fluid volume. Their survey found that monitoring of IOP during burn resuscitation is not routinely performed by the majority of providers. Taken together, the present study suggests clinical guidelines to recognize this complication of over-resuscitation.

Navigating the Postgraduate Research Fellowship: A Roadmap for Surgical Residents.

BACKGROUND: To preserve the future of surgical innovation, opportunities for surgical residents to receive structured research training are paramount. The objective of this article is to help surgical residents navigate a research fellowship by overviewing key topics such as choosing an area of focus and supervisor, applying for external funding, transitioning away from clinical duties, managing intellectual property, integrating family planning, and incorporating research experience into independent career development. MATERIALS AND METHODS: Using the framework of the University of Toronto's graduate degree-awarding Surgeon-Scientist Training Program, the authors outline key considerations, decisions, and pearls for surgical residents considering or currently enrolled in a full-time research fellowship training program. RESULTS: Full-time research fellowships offer a unique opportunity for residents interested in an academic career. Such full-time research fellowships away from clinical duties allow surgical trainees to focus on developing key research competencies, including how to generate hypotheses, apply research methodology, gain experience presenting and publishing manuscripts, and ultimately apply these skills as independent investigators to improve patient and population health. Research fellowships may also be an opportunity to develop intellectual property or facilitate family planning. Practical tips are provided for the transition back into clinical training and how to effectively market one's research skills for career advancement. CONCLUSIONS: The authors outline key considerations, decisions, and pearls for surgical residents considering or currently enrolled in a full-time research fellowship training program. By adhering to the principles highlighted in this article, residents will be able to successfully navigate a full-time research fellowship to optimize their intellectual development, maximize their academic productivity, and facilitate their transition into an independent investigator.

Electrical stimulation to enhance peripheral nerve regeneration: Update in molecular investigations and clinical translation.

Peripheral nerve injuries are common and frequently result in incomplete functional recovery even with optimal surgical treatment. Permanent motor and sensory deficits are associated with significant patient morbidity and socioeconomic burden. Despite substantial research efforts to enhance peripheral nerve regeneration, few effective and clinically feasible treatment options have been found. One promising strategy is the use of low frequency electrical stimulation delivered perioperatively to an injured nerve at the time of surgical repair. Possibly through its effect of increasing intraneuronal cyclic AMP, perioperative electrical stimulation accelerates axon outgrowth, remyelination of regenerating axons, and reinnervation of end organs, even with delayed surgical intervention. Building on decades of experimental evidence in animal models, several recent, prospective, randomized clinical trials have affirmed electrical stimulation as a clinically translatable technique to enhance functional recovery in patients with peripheral nerve injuries requiring surgical treatment. This paper provides an updated review of the cellular physiology of electrical stimulation and its effects on axon regeneration, Level I evidence from recent prospective randomized clinical trials of electrical stimulation, and ongoing and future directions of research into electrical stimulation as a clinically feasible adjunct to surgical intervention in the treatment of patients with peripheral nerve injuries.

Systemic and Local FK506 (Tacrolimus) and its Application in Peripheral Nerve Surgery.

Peripheral nerve injuries (PNI) are common and frequently afflict otherwise healthy individuals after traumatic or iatrogenic events. Adjuvant therapies to improve functional outcomes after surgical repair of PNI have been investigated extensively in preclinical studies; however, to date, none have been clinically proven to have a notable therapeutic effect. FK506 (tacrolimus), a US Food and Drug Administration-approved systemic immunosuppressant, has demonstrated promising neuro-regenerative properties in both animal studies and clinical reports, but its adverse effects when systemically administered have precluded its broader applicability for patients with PNI. Recent advances in bioengineered drug delivery systems have made local FK506 delivery to a site of PNI an intriguing method of promoting peripheral nerve regeneration, with promising results in preclinical translational investigations. This review summarizes the preclinical and clinical evidence for FK506's beneficial effect in promoting peripheral nerve regeneration when administered systemically and locally.

Evaluation of a Pediatric Facial Paralysis Education and Family Support Day.

INTRODUCTION: Facial paralysis impairs the mimetic functions of the facial musculature. In pediatric patients, free functioning muscle transfer neurotized with an intact contralateral facial nerve is the gold standard for smile reanimation. In response to requests from families of children with facial paralysis, the Division of Plastic and Reconstructive Surgery at the Hospital for Sick Children hosted an inaugural "Facial Paralysis Family Day." The objective was to create an opportunity for families to meet, exchange stories, and build support networks. METHODS: This study was a quality improvement project to conduct a needs assessment and evaluate the feasibility and satisfaction of implementing a family support intervention for individuals living with facial paralysis. RESULTS: The needs assessment demonstrated that families were most interested in advances in medicine, therapy and coping sessions and meeting other families. The post-event evaluation questionnaire indicated that attendees enjoyed the event, would attend again and found it highly valuable connecting and networking other families. It also indicated that key needs identified were addressed, with excellent ratings for the presentation discussing advances in medicine (100% rated "good" or "very good"), the therapy sessions (92% rated "good" or "very good") and the presentations by patients and their families (100% rated "good" or "very good.") DISCUSSION:: Two areas of improvement highlighted were elaborating further on medical advances and facilitating interactions between families. Overall, this event was well regarded and will likely be repeated at our institution and serve as a valuable resource for other hospitals planning to organize a similar event.

A single session of brief electrical stimulation enhances axon regeneration through nerve autografts.

Nerve graft reconstruction of gap defects may result in poor clinical outcomes, particularly with long regeneration distances. Electrical stimulation (ES) of nerves may improve outcomes in such patients. A single session of ES at 20 Hz for 1 h significantly enhances axon regeneration in animals and human subjects after nerve crush or nerve transection and repair. The objectives of this study were to evaluate if ES enhances axon regeneration through nerve grafts and if there is added benefit of a second, delayed session of ES (serial ES) on axon regeneration as compared to a single session only of ES. In female rats, a gap defect was created in the hindlimb common peroneal (CP) nerve and immediately reconstructed with a 10 mm nerve autograft (Experiment 1) or a 20 mm nerve autograft (Experiment 2). In Experiment 1, rats were randomized to 1 h of CP nerve ES or sham stimulation. In Experiment 2, rats were randomized to control (sham ES + sham ES), single ES (ES + sham ES), or serial ES (ES + ES), which consisted of an initial 1 h session of either ES or sham stimulation of the CP nerve, followed by a second 1 h session of ES or sham stimulation of the CP nerve 4 weeks later. In both experiments, after a 6 week period of nerve regeneration, CP neurons that had regenerated axons distal to the autograft were retrograde labelled for enumeration, and the CP nerve distal to the autograft was harvested for histomorphometry. In Experiment 1, rats that received CP nerve ES had statistically significantly more motor (p < .05) and sensory (p < .05) neurons that regenerated axons distal to the 10 mm nerve autograft, with more myelinated axons on histomorphometry (p < .001). Similarly, in Experiment 2, significantly more motor (p < .01) and sensory (p < .05) neurons regenerated axons distal to the 20 mm nerve autograft after a single session or two sessions of CP nerve ES. There was no significant difference in the number of regenerated motor or sensory neurons between rats with 20 mm CP nerve autografts receiving either one or two sessions of CP nerve ES (p > .05). In conclusion, a single session of ES enhances axon regeneration following nerve autografting with no added effect of a second, delayed session of ES. These findings support previous studies in animals and humans of the robust effect of a single session of ES in promoting nerve regeneration following injury and repair.