Polyethylene Glycol Fusion Restores Axonal Continuity and Improves Return of Function in a Rat Median Nerve Denervation Model.

BACKGROUND: Polyethylene glycol (PEG) can fuse severed closely-apposed axolemmas and restore axonal continuity. We evaluated the effects of PEG-fusion on functional recovery in a rodent forelimb model of peripheral nerve injury. METHODS: The median nerves of male Lewis rats (n=5 per group) were transected and repaired with standard suture repair (SR), SR with PEG (PEG), or SR with PEG and 1% methylene blue (PEG+MB); a sham surgery group was also included. Proximal stimulation produced compound nerve (CAPS) and muscle (CMAPs) action potentials recorded distally. The contralateral limb of each animal acted as an internal control for grip strength measurements. RESULTS: CAPs and CMAPs immediately returned in all PEG and PEG+MB animals, but not in SR animals. PEG and PEG+MB groups demonstrated earlier return of function by post-operative day (POD) 7 (62.6 ±7.3% and 50.9 ±6.7% of contralateral limb grip strength, respectively) compared to SR group, in which minimal return of function was not measurable until POD 21. At POD 98, the PEG group grip strength recovered to 77.2 ±2.8% while the PEG+MB grip strength recovered to 79.9 ±4.4%, compared to 34.9 ±1.8% recovery in the SR group (p<0.05). The PEG and PEG+MB groups reached 50% of the Sham group grip strength on POD 3.8 and 6.3, respectively, whereas the SR group did not reach 50% grip strength recovery of the Sham group throughout the study period. CONCLUSION: PEG-fusion plus neurorrhaphy with or without methylene blue re-established axonal continuity, shortened recovery time, and augmented functional recovery compared to suture neurorrhaphy alone.

Current Concepts in Lower Extremity Amputation: A Primer for Plastic Surgeons.

LEARNING OBJECTIVES: After studying this article, the participant should be able to: 1. Understand the goals of lower extremity reconstruction and identify clinical scenarios favoring amputation. 2. Understand lower extremity amputation physiology and biomechanics. 3. Review soft-tissue considerations to achieve durable coverage. 4. Appreciate the evolving management of transected nerves. 5. Highlight emerging applications of osseointegration and strategies to improve myoelectric prosthetic control. SUMMARY: Plastic surgeons are well versed in lower extremity reconstruction for traumatic, oncologic, and ischemic causes. Limb amputation is an increasingly sophisticated component of the reconstructive algorithm and is indicated when the residual limb is predicted to be more functional than a salvaged limb. Although plastic surgeons have traditionally focused on limb salvage, they play an increasingly vital role in optimizing outcomes from amputation. This warrants a review of core concepts and an update on emerging reconstructive techniques in amputee care.

The Effects of Growth Hormone on Nerve Regeneration and Alloimmunity in Vascularized Composite Allotransplantation.

BACKGROUND: Poor outcomes in functional recovery following upper extremity transplantation are largely due to denervation-induced muscle atrophy that occurs during the prolonged period of nerve regeneration. Growth hormone (GH) has well-established trophic effects on neurons, myocytes, and Schwann cells and represents a promising therapeutic approach to address this challenge. This study sought to confirm the positive effects of GH treatment on nerve regeneration and functional recovery and to evaluate the effects of GH treatment on the immune response in the setting of vascularized composite allotransplantation. METHODS: Rats underwent orthotopic forelimb transplantation across a full MHC-mismatch and received either porcine-derived growth hormone or no treatment (n=18 per group). Functional recovery was measured using electrically-stimulated grip strength testing. Animals were monitored for clinical and subclinical signs of rejection. RESULTS: Neuromuscular junction reinnervation and grip strength were improved in GH-treated animals (p=0.005; p=0.08). No statistically significant differences were seen in muscle atrophy, degree of myelination, axon diameter, and axon counts between groups. The rates of clinical and histological rejection did not significantly differ among groups. CONCLUSIONS: Our findings alleviate concern for increased risk of transplant rejection during GH therapy and therefore support the translation of growth hormone as a therapeutic method to promote improved functional recovery in upper extremity transplantation.

Translational bioengineering strategies for peripheral nerve regeneration: opportunities, challenges, and novel concepts.

Peripheral nerve injuries remain a challenging problem in need of better treatment strategies. Despite best efforts at surgical reconstruction and postoperative rehabilitation, patients are often left with persistent, debilitating motor and sensory deficits. There are currently no therapeutic strategies proven to enhance the regenerative process in humans. A clinical need exists for the development of technologies to promote nerve regeneration and improve functional outcomes. Recent advances in the fields of tissue engineering and nanotechnology have enabled biomaterial scaffolds to modulate the host response to tissue repair through tailored mechanical, chemical, and conductive cues. New bioengineered approaches have enabled targeted, sustained delivery of protein therapeutics with the capacity to unlock the clinical potential of a myriad of neurotrophic growth factors that have demonstrated promise in enhancing regenerative outcomes. As such, further exploration of combinatory strategies leveraging these technological advances may offer a pathway towards clinically translatable solutions to advance the care of patients with peripheral nerve injuries. This review first presents the various emerging bioengineering strategies that can be applied for the management of nerve gap injuries. We cover the rationale and limitations for their use as an alternative to autografts, focusing on the approaches to increase the number of regenerating axons crossing the repair site, and facilitating their growth towards the distal stump. We also discuss the emerging growth factor-based therapeutic strategies designed to improve functional outcomes in a multimodal fashion, by accelerating axonal growth, improving the distal regenerative environment, and preventing end-organs atrophy.

A Systematic Review of Muscle Synergies during a Walking Gait to Define Optimal Donor-Recipient Pairings for Lower Extremity Functional Reconstruction.

Functional lower extremity reconstruction primarily aims to restore independent ambulation. We sought to define the synergies recruited during a walking gait to inform donor selection for various motor deficits. With these findings, we discuss the functional neuromuscular components of independent gait with the goal of informing lower extremity reconstruction. Methods: A systematic review was performed using MEDLINE for articles published between January 2000 and December 2020. Search terms included (1) "motor module(s)," "synergy," "motor pattern," or "motor primitive" and (2) "gait," "walking," "ambulation," or "locomotion." Abstracts/full texts were reviewed by two independent reviewers. Results: A total of 38 studies were selected. The average reported number of synergies and variance accounted for was 4.5 ± 0.9 and 88.6% ± 7.7%, respectively. Four motor modules were conserved across nearly all studies. Conclusions: Walking can be reduced to the sequential activation of four motor modules. Activities during the stance phase are critical for both standing stability and forward progression and should be prioritized for reconstruction with the goal of preserving efficient gait. Muscles recruited during swing, except those used for ankle dorsiflexion, are less prone to injury and benefit from greater redundancy, less often necessitating reconstruction. With the emphasis on stability during stance, several synergistic or sometimes even antagonistic tendons can be used to replace their counterparts and restore efficient, independent ambulation. With a finite supply of donor tissues, and in the absence of well-defined clinical outcomes data, this research allows us to effectively prioritize reconstructive goals and maximize patient outcomes.

A critical analysis of American insurance coverage for imaging and surgical treatment of lymphedema.

BACKGROUND: Over 35 million Americans have lymphedema. Nonetheless, lymphedema is underdiagnosed and undertreated worldwide. We investigated whether the rates of coverage for imaging and surgical procedures may contribute to the limited care provided for lymphedema. METHODS: We performed a cross-sectional evaluation of 58 insurers, chosen based on state enrollment and market share. A web-based search or phone call determined whether a publicly available policy on lymphedema-specific imaging, physiological procedures, and excisional procedures was available. Coverage status and corresponding criteria were extracted. RESULTS: Of the two-thirds of insurers who included a policy on imaging, 4% (n = 2) provided coverage and 4% (n = 2) specified coverage only on a case-by-case basis. Forty-eight percent (n = 28) of insurers had a statement of coverage on lymphovenous bypass or vascularized lymph node transfer, in which reimbursement was almost universally denied (96%, n = 26; 93%, n = 26). Liposuction and debulking procedures were included in 25 (43%) and 13 (22%) policies, in which seven (28%) and four (31%) insurers would provide coverage, with over 75% having criteria. Coverage of liposuction was significantly more than for lymphovenous bypass (P < .04). CONCLUSIONS: Nearly one-half of American insurers do not have a publicly available policy on most imaging, physiological, or excisional procedures, leaving coverage status ambiguous. Reimbursement was uncommon for imaging and physiological procedures, whereas the majority of insurers who did offer coverage for excisional procedures also had multiple criteria to be met. These elements may together be a limiting factor in receiving appropriate care for lymphedema.

A review of American insurance coverage and criteria for conservative management of lymphedema.

OBJECTIVE: Lymphedema affects >1 in 1000 Americans, most often resulting from breast cancer surgery. Conservative treatment, such as compression garments, combined decongestive therapy (CDT), and pneumatic compression pumps, is the current standard of care. Despite the wide availability of these therapies, lymphedema has remained undertreated worldwide. We investigated whether third-party insurance coverage might be a barrier to obtaining conservative treatment in the United States. METHODS: We conducted a cross-sectional analysis of publicly accessible insurance policies. A total of 58 insurers were included in accordance with their state enrollment data and market share. The analysis was conducted using a web-based search and individual telephone interviews. For those policies that extended coverage, the medical necessity criteria were abstracted. RESULTS: A total of 50 insurance companies (86%) had a policy in place addressing conservative management. Included in 37 policies (64%), compression garments were covered the least often (n = 33; 89%). Although CDT was included in only 22 policies (38%), it was universally covered. Noncalibrated pneumatic compression pumps were the most frequently addressed intervention (n = 46; 79%), significantly more often than CDT (P < .01) and were universally covered, significantly more often than were compression garments (P < .04). Criteria for reimbursement were present for more than one half of the policies that provided coverage. CONCLUSIONS: A large proportion of U.S. insurers provided coverage for conservative treatment of lymphedema. However, only 38% of the policies included a statement of coverage for CDT. Most of the policies that did provide coverage for these four therapies also had multiple criteria that were required to be met before considering reimbursement. These requirements could create barriers to the receipt of treatment.

Wound Closure with Transcutaneous Absorbable Polyglactin Sutures after Hidradenitis Suppurativa Excision.

OBJECTIVE: Wide surgical excision is the standard treatment for severe hidradenitis suppurativa (HS). Because of the nature of HS, these wounds are often nonsterile, located in moist intertriginous regions, and closed under tension, increasing the risk for surgical site complications. Although uncommon, absorbable sutures may confer benefits over nonabsorbable material for skin closure. Accordingly, the authors evaluated the use of absorbable, braided, transcutaneous polyglactin sutures after wide surgical excision of HS. METHODS: The authors performed a retrospective chart review for all consecutive patients who underwent wide surgical excision of HS at a tertiary university hospital between January 2009 and March 2020. RESULTS: Sixty consecutive patients with 174 operative sites were included in the study. The surgical site complication rate was 17.8%. Postoperative complications included wound dehiscence (n = 18), surgical site infection (n = 2), and scar contracture (n = 1). Sutures were removed from 12 (6.9%) operative sites. Factors influencing complications were Hurley grade and area of excision. Complications did not differ significantly among disease locations (P = .6417). CONCLUSIONS: The results support the growing evidence that absorbable sutures are an appropriate option after wide surgical excision of HS.

Sustained IGF-1 delivery ameliorates effects of chronic denervation and improves functional recovery after peripheral nerve injury and repair.

Functional recovery following peripheral nerve injury is limited by progressive atrophy of denervated muscle and Schwann cells (SCs) that occurs during the long regenerative period prior to end-organ reinnervation. Insulin-like growth factor 1 (IGF-1) is a potent mitogen with well-described trophic and anti-apoptotic effects on neurons, myocytes, and SCs. Achieving sustained, targeted delivery of small protein therapeutics remains a challenge. We hypothesized that a novel nanoparticle (NP) delivery system can provide controlled release of bioactive IGF-1 targeted to denervated muscle and nerve tissue to achieve improved motor recovery through amelioration of denervation-induced muscle atrophy and SC senescence and enhanced axonal regeneration. Biodegradable NPs with encapsulated IGF-1/dextran sulfate polyelectrolyte complexes were formulated using a flash nanoprecipitation method to preserve IGF-1 bioactivity and maximize encapsulation efficiencies. Under optimized conditions, uniform PEG-b-PCL NPs were generated with an encapsulation efficiency of 88.4%, loading level of 14.2%, and a near-zero-order release of bioactive IGF-1 for more than 20 days in vitro. The effects of locally delivered IGF-1 NPs on denervated muscle and SCs were assessed in a rat median nerve transection-without- repair model. The effects of IGF-1 NPs on axonal regeneration, muscle atrophy, reinnervation, and recovery of motor function were assessed in a model in which chronic denervation is induced prior to nerve repair. IGF-1 NP treatment resulted in significantly greater recovery of forepaw grip strength, decreased denervation-induced muscle atrophy, decreased SC senescence, and improved neuromuscular reinnervation.

Vascularized, Denervated Muscle Targets for Treatment of Symptomatic Neuromas in the Upper Extremity: Description of Operative Technique.

Symptomatic neuromas of the upper extremity often cause persistent, debilitating pain that is resistant to medical management. Following upper extremity amputation, painful neuromas may disrupt rehabilitation efforts and pose a barrier to prosthetic use. Several surgical approaches have been attempted to treat neuromas, each of which suffers from limitations. We have developed a novel technique, the vascularized, denervated muscle target, that offers a compelling new option for primary prevention and secondary treatment of symptomatic neuromas of the upper extremity. Here, we provide a detailed description of our surgical technique as it is applied to neuromas of the upper extremity.

Utility of Viscoelastic Tests to Predict Flap Thrombosis: A Systematic Review.

BACKGROUND: Flap thrombosis is a rare but devastating complication in microsurgery. Preoperative identification of patients at increased risk for microvascular thrombosis remains challenging. Viscoelastic testing (VET) provides a comprehensive evaluation of the clotting process and can effectively identify hypercoagulability. However, the utility of VET in microvascular reconstruction remains unclear. METHODS: A systematic review of the association between VET and pedicle thrombosis and free flap loss was performed in accordance with Preferred Reporting Items for Systematic Reviews (PRISMA) guidelines. Identified studies were reviewed independently by two authors for pertinent data. RESULTS: Six studies met inclusion criteria. Heterogenous study design and outcome reporting complicated direct comparisons and precluded a formal meta-analysis. Four studies found a statistically significant relationship between VET results and flap thrombosis or flap loss. The maximum clot strength and the fibrinogen-to-platelet ratio (FPR) were key viscoelastic parameters in these studies, both representing a measure of maximal clot strength. Specifically, an elevated FPR (>42%) generated a sensitivity and specificity for flap loss ranging from 57% to 75% and 60% to 82%, respectively. Notably, the negative predictive value for flap failure with a normal preoperative FPR was greater than 90% in all studies reporting a correlation. The remaining two studies reported no predictive value for VET with respect to flap failure or pedicle thrombosis. CONCLUSION: The results of this review suggest that VET, particularly parameters relating to clot strength, may help clinicians identify patients at risk for flap thrombosis. However, uncontrolled and heterogenous reporting limit definitive conclusions, and high-quality diagnostic studies are needed to better determine the clinical utility of viscoelastic testing for free flap patients.

The Effects of a Porcine Extracellular Matrix Nerve Wrap as an Adjunct to Primary Epineurial Repair.

PURPOSE: Outcomes after end-to-end epineural suture repair remain poor. Nerve wraps have been advocated to improve regeneration across repair sites by potentially reducing axonal escape and scar ingrowth; however, limited evidence currently exists to support their use. METHODS: Forty Lewis rats underwent median nerve division and immediate repair. Half were repaired with epineural suturing alone, and the others underwent epineural suture repair with the addition of a nerve wrap. Motor recovery was measured using weekly grip strength and nerve conduction testing for 15 weeks. Histomorphometric analyses were performed to assess intraneural collagen deposition, cellular infiltration, and axonal organization at the repair site, as well as axonal regeneration and neuromuscular junction reinnervation distal to the repair site. RESULTS: The wrapped group demonstrated significantly less intraneural collagen deposition at 5 weeks. Axonal histomorphometry, cellular infiltration, neuromuscular junction reinnervation, and functional recovery did not differ between groups. CONCLUSIONS: Nerve wraps reduced collagen deposition within the coaptation; however, no differences were observed in axonal regeneration, neuromuscular junction reinnervation, or functional recovery. CLINICAL RELEVANCE: These findings suggest that extracellular matrix nerve wraps can attenuate scar deposition at the repair site. Any benefits that may exist with regards to axonal regeneration and functional recovery were not detected in our model.

A Surgical Approach to Treat Painful Neuromas of the Supraorbital and Supratrochlear Nerves with Implantation of the Proximal Stump into the Orbit.

Frontal neuralgia causally related to trauma to the supraorbital and supratrochlear nerves remains a difficult problem to resolve. A peripheral nerve approach to this problem would involve neuroma resection and relocation of the proximal nerve stump to a location away from the vulnerable supraorbital ridge. A retrospective chart review was done to identify patients with frontal pain related to supraorbital trauma who underwent operative interventions to solve this problem by neuroma resection and relocation of the proximal stumps into the orbit. Eight patients were identified for inclusion in this study. At a mean of 16 months after surgery, there was a significant change in the visual analog score from a mean of 9.4 to 2.8 ( p < 0.05), with 88% of the patients reporting a >50% reduction in pain postoperatively. There was one treatment failure. There were no postoperative complications. The strategy of relocating the proximal end of the supraorbital and supratrochlear nerves into the posterior orbit after resecting the painful neuromas can successfully manage posttraumatic craniofacial pain related to these injured nerves.

Stimulated grip strength measurement: Validation of a novel method for functional assessment.

BACKGROUND: Reliable measurement of functional recovery is critical in translational peripheral nerve regeneration research. Behavioral functional assessments such as volitional grip strength testing (vGST) are limited by inherent behavioral variability. Isometric tetanic force testing (ITFT) is highly reliable but precludes serial measurements. Combining elements of vGST and ITFT, stimulated grip strength testing (sGST) involves percutaneous median nerve stimulation to elicit maximal tetanic contraction of digital flexors, thereby allowing for consistent measurement of maximal grip strength. METHODS: We measured side-to-side equivalence of force using sGST, vGST, and ITFT to determine relative reliability and repeatability. We also performed weekly force measurements following median nerve repair. RESULTS: sGST demonstrated greater reliability and inter-trial repeatability than vGST and similar reliability to ITFT, with the added benefit of serial measurements. CONCLUSIONS: sGST is a valid method for assessing functional recovery that addresses the limitations of the currently available modalities used in translational peripheral nerve regeneration research.

Is There a Limit? A Risk Assessment Model of Liposuction and Lipoaspirate Volume on Complications in Abdominoplasty.

BACKGROUND: Combining liposuction and abdominoplasty is controversial because of concerns for increased complications and potential for vascular compromise of the abdominoplasty flap. Also, the lipoaspirate volume in abdominoplasty is regulated in some areas to as little as 500 ml when performed with abdominoplasty. This study measures abdominoplasty complication rates when performed with and without trunk liposuction, and evaluates the effect of lipoaspirate volume on complications. METHODS: Abdominoplasty and liposuction of the trunk procedures were identified in the Tracking Operations and Outcomes for Plastic Surgeons database. Multivariate regression models determined the effect of liposuction with abdominoplasty on complications compared with abdominoplasty alone and determined the effect of liposuction volume on complications. RESULTS: Eleven thousand one hundred ninety-one patients were identified: 9638 (86.1 percent) having abdominoplasty with truncal liposuction and 1553 (13.9 percent) having abdominoplasty alone. Overall complication rates were 10.5 percent and 13.0 percent, respectively. Combined liposuction and abdominoplasty was independently associated with a reduced risk of both overall complications (p = 0.046) and seroma (p = 0.030). Given existing laws limiting liposuction volume to 500 or 1000 ml in combination with abdominoplasty, each of these thresholds was evaluated, with no effect on complications. Surprisingly, increasing liposuction volume was not independently associated with an increased risk of any complication. CONCLUSIONS: When done by board-certified plastic surgeons, abdominoplasty with truncal liposuction is safe, with fewer complications than abdominoplasty alone. Regulations governing liposuction volumes in abdominoplasty are arbitrary and do not reflect valid thresholds for increased complications. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Donor-site Morbidity of Medial and Lateral Thigh-based Flaps: A Comparative Study.

BACKGROUND: Free and pedicled medial and lateral thigh-based flaps are common reconstructive procedures. However, there have been no comparative studies of morbidity between medial and lateral donor sites. METHODS: We conducted an Enterprise Data Warehouse-based review of all the senior authors' (R.D.G., G.A.D., and M.S.A.) thigh-based free and pedicled flaps. Patient demographic data, donor-site complications, drain duration, and number of postoperative visits were collected and compared. Complications were also compared between fasciocutaneous flaps and muscle or myocutaneous flaps, and skin grafted donor sites. RESULTS: We analyzed 352 flap donor sites, with 155 medial and 197 lateral. Two hundred seventeen (217) flaps were pedicled. Flap types included 127 gracilis, 27 rectus femoris, 134 anterolateral thigh, and 36 vastus lateralis-only flaps. There were no significant differences in complications between medial (17.4%) and lateral thigh (21.3%) donor sites, although lateral thigh flaps had a mean of 1 additional postoperative visit. Rates of wound dehiscence/healing issues were significantly higher in both gracilis myocutaneous flaps (25.9%) and flaps requiring a skin grafted donor site (31.2%). Postoperative therapeutic anticoagulation was the only significant risk factor for a donor-site complication. Flap complications resulted in increased drain duration and postoperative office visits. CONCLUSIONS: Donor-site morbidity is similar in both lateral and medial thigh-based flaps. The inclusion of muscle in the flap from either donor site does not seem to increase complications, but the inclusion of a skin paddle with gracilis muscle, or a skin grafted lateral thigh donor site, results in increased wound healing complications.

Evaluating the Rule of 10s in Cleft Lip Repair: Do Data Support Dogma?

BACKGROUND: Cleft lip represents one of the most common birth defects in the world. Although the timing of cleft lip repair is contingent on a number of factors, the "rule of 10s" remains a frequently quoted safety benchmark. Initially reported by Wilhelmsen and Musgrave in 1966 and modified by Millard in 1976, this rule referred to performing surgery once patients had reached cutoffs in weight, hemoglobin, and age/leukocyte count. Despite significant advances in both surgical and anesthetic technique, the oft-quoted "rule of 10s" has not been systematically investigated since its inception. METHODS: Patients who underwent primary cleft lip repair were identified from the National Surgical Quality Improvement Program Pediatric database. Multivariate logistic regression models were used to determine the independent effect of each rule of 10 metric or violation of the rule of 10s as a whole on postoperative complications, and to determine independent risk factors for complications in cleft lip surgery. RESULTS: One thousand three hundred thirteen patients met inclusion criteria, with a 3.6 percent complication rate. Of the included patients, 151 (11.5 percent) violated at least one facet of the rule of 10s. Other than patient weight, neither the rule of 10s nor any individual metric was significantly predictive of postoperative complications. CONCLUSIONS: Since its introduction nearly a half century ago, the risks associated with performing surgery in patients who violate the rule of 10s has undergone dramatic reductions. This analysis highlights the need to continually validate and evaluate dogma as the field continues to advance. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.

Predictors of 30-day readmission after mastectomy: A multi-institutional analysis of 21,271 patients.

BACKGROUND: Recent healthcare legislation has made unplanned hospital readmission an important metric of health care quality, and current efforts center on reducing this complication in order to avoid fiduciary penalties. OBJECTIVE: There is currently a paucity of data delineating risk factors for readmission following mastectomy. To this end, we sought to develop a predictive model of unplanned readmissions following mastectomy. METHODS: The 2011 and 2012 National Surgical Quality Improvement Program (NSQIP) datasets were retrospectively queried to identify patients who underwent mastectomy. Multivariate logistic regression modeling was used to identify risk factors for readmission. RESULTS: Of 21,271 patients meeting inclusion criteria, 1,190 (5.59%) were readmitted. The most commonly cited reasons for readmission included surgical site complications (32.85%), infection not localized to the surgical site (2.72%), and venous thromboembolism (4.39%). Independent predictors of readmission included BMI, active smoking status, and skin-sparing mastectomy. Significantly, concurrent breast reconstruction and bilateral mastectomy were not independent predictors of readmission. CONCLUSIONS: This is the first study of readmission rates after mastectomy. Awareness of specific risk factors for readmission, particularly those that are modifiable, may serve to identify and manage high risk patients, aid in the development of pre- and postoperative clinical care guidelines, and ultimately improve patient care.